Inflammation and fibrosis in murine models of heart failure

  • Lucas BacmeisterEmail author
  • Michael Schwarzl
  • Svenja Warnke
  • Bastian Stoffers
  • Stefan Blankenberg
  • Dirk Westermann
  • Diana LindnerEmail author


Heart failure is a consequence of various cardiovascular diseases and associated with poor prognosis. Despite progress in the treatment of heart failure in the past decades, prevalence and hospitalisation rates are still increasing. Heart failure is typically associated with cardiac remodelling. Here, inflammation and fibrosis are thought to play crucial roles. During cardiac inflammation, immune cells invade the cardiac tissue and modulate tissue-damaging responses. Cardiac fibrosis, however, is characterised by an increased amount and a disrupted composition of extracellular matrix proteins. As evidence exists that cardiac inflammation and fibrosis are potentially reversible in experimental and clinical set ups, they are interesting targets for innovative heart failure treatments. In this context, animal models are important as they mimic clinical conditions of heart failure patients. The advantages of mice in this respect are short generation times and genetic modifications. As numerous murine models of heart failure exist, the selection of a proper disease model for a distinct research question is demanding. To facilitate this selection, this review aims to provide an overview about the current understanding of the pathogenesis of cardiac inflammation and fibrosis in six frequently used murine models of heart failure. Hence, it compares the models of myocardial infarction with or without reperfusion, transverse aortic constriction, chronic subjection to angiotensin II or deoxycorticosterone acetate, and coxsackievirus B3-induced viral myocarditis in this context. It furthermore provides information about the clinical relevance and the limitations of each model, and, if applicable, about the recent advancements in their methodological proceedings.


Myocardial infarction (MI) Ischemia/reperfusion Pressure overload Cardiac hypertrophy Neurohumoral activation Myocarditis 



The authors thank Katharina Scherschel for excellent help and support in microscopic imaging techniques.

Author contributions

All authors listed have made a substantial, direct and intellectual contribution to the work and approved the manuscript for publication.


This work was funded by the German Ministry of Research and Education (DZHK, German Center of Cardiovascular Research), Grant number 81365-150.

Compliance with ethical standards

Conflict of interest

The authors declare no conflict of interest.


  1. 1.
    Aartsen WM, Pelsers MM, Hermens WT, Glatz JF, Daemen MJ, Smits JF (2000) Heart fatty acid binding protein and cardiac troponin T plasma concentrations as markers for myocardial infarction after coronary artery ligation in mice. Pflugers Arch 439:416–422. CrossRefPubMedGoogle Scholar
  2. 2.
    Adiarto S, Heiden S, Vignon-Zellweger N, Nakayama K, Yagi K, Yanagisawa M, Emoto N (2012) ET-1 from endothelial cells is required for complete angiotensin II-induced cardiac fibrosis and hypertrophy. Life Sci 91:651–657. CrossRefPubMedGoogle Scholar
  3. 3.
    Alard JE, Ortega-Gomez A, Wichapong K, Bongiovanni D, Horckmans M, Megens RT, Leoni G, Ferraro B, Rossaint J, Paulin N, Ng J, Ippel H, Suylen D, Hinkel R, Blanchet X, Gaillard F, D’Amico M, von Hundelshausen P, Zarbock A, Scheiermann C, Hackeng TM, Steffens S, Kupatt C, Nicolaes GA, Weber C, Soehnlein O (2015) Recruitment of classical monocytes can be inhibited by disturbing heteromers of neutrophil HNP1 and platelet CCL5. Sci Transl Med 7:317ra196. CrossRefPubMedGoogle Scholar
  4. 4.
    Alex L, Frangogiannis NG (2018) The cellular origin of activated fibroblasts in the infarcted and remodeling myocardium. Circ Res 122:540–542. CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Andersson L, Scharin Tang M, Lundqvist A, Lindbom M, Mardani I, Fogelstrand P, Shahrouki P, Redfors B, Omerovic E, Levin M, Boren J, Levin MC (2015) Rip2 modifies VEGF-induced signalling and vascular permeability in myocardial ischaemia. Cardiovasc Res 107:478–486. CrossRefPubMedGoogle Scholar
  6. 6.
    Annes JP, Munger JS, Rifkin DB (2003) Making sense of latent TGFbeta activation. J Cell Sci 116:217–224. CrossRefPubMedGoogle Scholar
  7. 7.
    Anzini M, Merlo M, Sabbadini G, Barbati G, Finocchiaro G, Pinamonti B, Salvi A, Perkan A, Di Lenarda A, Bussani R, Bartunek J, Sinagra G (2013) Long-term evolution and prognostic stratification of biopsy-proven active myocarditis. Circulation 128:2384–2394. CrossRefPubMedGoogle Scholar
  8. 8.
    Arola A, Kalimo H, Ruuskanen O, Hyypia T (1995) Experimental myocarditis induced by two different coxsackievirus B3 variants: aspects of pathogenesis and comparison of diagnostic methods. J Med Virol 47:251–259. CrossRefPubMedGoogle Scholar
  9. 9.
    Arslan F, Smeets MB, Riem Vis PW, Karper JC, Quax PH, Bongartz LG, Peters JH, Hoefer IE, Doevendans PA, Pasterkamp G, de Kleijn DP (2011) Lack of fibronectin-EDA promotes survival and prevents adverse remodeling and heart function deterioration after myocardial infarction. Circ Res 108:582–592. CrossRefPubMedGoogle Scholar
  10. 10.
    Badorff C, Lee GH, Lamphear BJ, Martone ME, Campbell KP, Rhoads RE, Knowlton KU (1999) Enteroviral protease 2A cleaves dystrophin: evidence of cytoskeletal disruption in an acquired cardiomyopathy. Nat Med 5:320–326. CrossRefPubMedGoogle Scholar
  11. 11.
    Baicu CF, Zhang YH, Van Laer AO, Renaud L, Zile MR, Bradshaw AD (2012) Effects of the absence of procollagen C-endopeptidase enhancer-2 on myocardial collagen accumulation in chronic pressure overload. Am J Physiol Heart Circ Physiol 303:H234–H240. CrossRefPubMedPubMedCentralGoogle Scholar
  12. 12.
    Barcellos-Hoff MH, Derynck R, Tsang ML, Weatherbee JA (1994) Transforming growth factor-beta activation in irradiated murine mammary gland. J Clin Investig 93:892–899. CrossRefPubMedGoogle Scholar
  13. 13.
    Barrick CJ, Dong AP, Waikel R, Corn D, Yang F, Threadgill DW, Smyth SS (2009) Parent-of-origin effects on cardiac response to pressure overload in mice. Am J Physiol Heart Circ Physiol 297:H1003–H1009. CrossRefPubMedPubMedCentralGoogle Scholar
  14. 14.
    Basting T, Lazartigues E (2017) DOCA-salt hypertension: an update. Curr Hypertens Rep 19:32. CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Becher PM, Gotzhein F, Klingel K, Escher F, Blankenberg S, Westermann D, Lindner D (2017) Cardiac function remains impaired despite reversible cardiac remodeling after acute experimental viral myocarditis. J Immunol Res 2017:6590609. CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Becher PM, Hinrichs S, Fluschnik N, Hennigs JK, Klingel K, Blankenberg S, Westermann D, Lindner D (2018) Role of Toll-like receptors and interferon regulatory factors in different experimental heart failure models of diverse etiology: IRF7 as novel cardiovascular stress-inducible factor. PLoS One 13:e0193844. CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Becher PM, Lindner D, Miteva K, Savvatis K, Zietsch C, Schmack B, Van Linthout S, Westermann D, Schultheiss HP, Tschope C (2012) Role of heart rate reduction in the prevention of experimental heart failure: comparison between If-channel blockade and beta-receptor blockade. Hypertension 59:949–957. CrossRefPubMedGoogle Scholar
  18. 18.
    Bhattacharya K, Farwell K, Huang M, Kempuraj D, Donelan J, Papaliodis D, Vasiadi M, Theoharides TC (2007) Mast cell deficient W/Wv mice have lower serum IL-6 and less cardiac tissue necrosis than their normal littermates following myocardial ischemia-reperfusion. Int J Immunopathol Pharmacol 20:69–74. CrossRefPubMedGoogle Scholar
  19. 19.
    Bliksoen M, Mariero LH, Torp MK, Baysa A, Ytrehus K, Haugen F, Seljeflot I, Vaage J, Valen G, Stenslokken KO (2016) Extracellular mtDNA activates NF-kappaB via toll-like receptor 9 and induces cell death in cardiomyocytes. Basic Res Cardiol 111:42. CrossRefPubMedGoogle Scholar
  20. 20.
    Brown LF, Dubin D, Lavigne L, Logan B, Dvorak HF, Van de Water L (1993) Macrophages and fibroblasts express embryonic fibronectins during cutaneous wound healing. Am J Pathol 142:793–801PubMedPubMedCentralGoogle Scholar
  21. 21.
    Brown RD, Ambler SK, Mitchell MD, Long CS (2005) The cardiac fibroblast: therapeutic target in myocardial remodeling and failure. Annu Rev Pharmacol Toxicol 45:657–687. CrossRefPubMedGoogle Scholar
  22. 22.
    Bujak M, Dobaczewski M, Chatila K, Mendoza LH, Li N, Reddy A, Frangogiannis NG (2008) Interleukin-1 receptor type I signaling critically regulates infarct healing and cardiac remodeling. Am J Pathol 173:57–67. CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Bujak M, Frangogiannis NG (2007) The role of TGF-beta signaling in myocardial infarction and cardiac remodeling. Cardiovasc Res 74:184–195. CrossRefPubMedGoogle Scholar
  24. 24.
    Camacho Londono JE, Tian Q, Hammer K, Schroder L, Camacho Londono J, Reil JC, He T, Oberhofer M, Mannebach S, Mathar I, Philipp SE, Tabellion W, Schweda F, Dietrich A, Kaestner L, Laufs U, Birnbaumer L, Flockerzi V, Freichel M, Lipp P (2015) A background Ca2+ entry pathway mediated by TRPC1/TRPC4 is critical for development of pathological cardiac remodelling. Eur Heart J 36:2257–2266. CrossRefPubMedPubMedCentralGoogle Scholar
  25. 25.
    Chandrasekar B, Marelli-Berg FM, Tone M, Bysani S, Prabhu SD, Murray DR (2004) Beta-adrenergic stimulation induces interleukin-18 expression via beta2-AR, PI3 K, Akt, IKK, and NF-kappaB. Biochem Biophys Res Commun 319:304–311. CrossRefPubMedGoogle Scholar
  26. 26.
    Chen B, Frangogiannis NG (2018) The role of macrophages in nonischemic heart failure. JACC Basic Transl Sci 3:245–248. CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Chen H, Hwang H, McKee LA, Perez JN, Regan JA, Constantopoulos E, Lafleur B, Konhilas JP (2013) Temporal and morphological impact of pressure overload in transgenic FHC mice. Front Physiol 4:205. CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Chen W, Spitzl A, Mathes D, Nikolaev VO, Werner F, Weirather J, Spiranec K, Rock K, Fischer JW, Kammerer U, Stegner D, Baba HA, Hofmann U, Frantz S, Kuhn M (2016) Endothelial actions of ANP enhance myocardial inflammatory infiltration in the early phase after acute infarction. Circ Res 119:237–248. CrossRefPubMedGoogle Scholar
  29. 29.
    Chow LH, Beisel KW, McManus BM (1992) Enteroviral infection of mice with severe combined immunodeficiency. Evidence for direct viral pathogenesis of myocardial injury. Lab Invest 66:24–31PubMedGoogle Scholar
  30. 30.
    Cimini M, Fazel S, Zhuo S, Xaymardan M, Fujii H, Weisel RD, Li RK (2007) c-kit dysfunction impairs myocardial healing after infarction. Circulation 116:I77–I82. CrossRefPubMedGoogle Scholar
  31. 31.
    Cleutjens JP, Verluyten MJ, Smiths JF, Daemen MJ (1995) Collagen remodeling after myocardial infarction in the rat heart. Am J Pathol 147:325–338PubMedPubMedCentralGoogle Scholar
  32. 32.
    Cochain C, Channon KM, Silvestre JS (2013) Angiogenesis in the infarcted myocardium. Antioxid Redox Signal 18:1100–1113. CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Cohen M, Boiangiu C, Abidi M (2010) Therapy for ST-segment elevation myocardial infarction patients who present late or are ineligible for reperfusion therapy. J Am Coll Cardiol 55:1895–1906. CrossRefPubMedGoogle Scholar
  34. 34.
    Cooper LT Jr (2009) Myocarditis. N Engl J Med 360:1526–1538. CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Corbett SA, Schwarzbauer JE (1998) Fibronectin-fibrin cross-linking: a regulator of cell behavior. Trends Cardiovasc Med 8:357–362. CrossRefPubMedGoogle Scholar
  36. 36.
    Creemers E, Cleutjens J, Smits J, Heymans S, Moons L, Collen D, Daemen M, Carmeliet P (2000) Disruption of the plasminogen gene in mice abolishes wound healing after myocardial infarction. Am J Pathol 156:1865–1873. CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Dai DF, Johnson SC, Villarin JJ, Chin MT, Nieves-Cintron M, Chen T, Marcinek DJ, Dorn GW 2nd, Kang YJ, Prolla TA, Santana LF, Rabinovitch PS (2011) Mitochondrial oxidative stress mediates angiotensin II-induced cardiac hypertrophy and Galphaq overexpression-induced heart failure. Circ Res 108:837–846. CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    de Lucia C, Eguchi A, Koch WJ (2018) New insights in cardiac beta-adrenergic signaling during heart failure and aging. Front Pharmacol 9:904. CrossRefPubMedPubMedCentralGoogle Scholar
  39. 39.
    DeLeon-Pennell KY, Iyer RP, Ero OK, Cates CA, Flynn ER, Cannon PL, Jung M, Shannon D, Garrett MR, Buchanan W, Hall ME, Ma Y, Lindsey ML (2017) Periodontal-induced chronic inflammation triggers macrophage secretion of Ccl12 to inhibit fibroblast-mediated cardiac wound healing. JCI Insight. CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    Deschamps AM, Spinale FG (2006) Pathways of matrix metalloproteinase induction in heart failure: bioactive molecules and transcriptional regulation. Cardiovasc Res 69:666–676. CrossRefPubMedGoogle Scholar
  41. 41.
    Desmouliere A, Geinoz A, Gabbiani F, Gabbiani G (1993) Transforming growth factor-beta 1 induces alpha-smooth muscle actin expression in granulation tissue myofibroblasts and in quiescent and growing cultured fibroblasts. J Cell Biol 122:103–111. CrossRefPubMedGoogle Scholar
  42. 42.
    Dewald O, Frangogiannis NG, Zoerlein MP, Duerr GD, Taffet G, Michael LH, Welz A, Entman ML (2004) A murine model of ischemic cardiomyopathy induced by repetitive ischemia and reperfusion. Thorac Cardiovasc Surg 52:305–311. CrossRefPubMedGoogle Scholar
  43. 43.
    Dewald O, Ren G, Duerr GD, Zoerlein M, Klemm C, Gersch C, Tincey S, Michael LH, Entman ML, Frangogiannis NG (2004) Of mice and dogs: species-specific differences in the inflammatory response following myocardial infarction. Am J Pathol 164:665–677. CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Dobaczewski M, Bujak M, Zymek P, Ren G, Entman ML, Frangogiannis NG (2006) Extracellular matrix remodeling in canine and mouse myocardial infarcts. Cell Tissue Res 324:475–488. CrossRefPubMedGoogle Scholar
  45. 45.
    Dobaczewski M, Gonzalez-Quesada C, Frangogiannis NG (2010) The extracellular matrix as a modulator of the inflammatory and reparative response following myocardial infarction. J Mol Cell Cardiol 48:504–511. CrossRefPubMedGoogle Scholar
  46. 46.
    Duerrschmid C, Crawford JR, Reineke E, Taffet GE, Trial J, Entman ML, Haudek SB (2013) TNF receptor 1 signaling is critically involved in mediating angiotensin-II-induced cardiac fibrosis. J Mol Cell Cardiol 57:59–67. CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Dunlay SM, Roger VL, Weston SA, Jiang R, Redfield MM (2012) Longitudinal changes in ejection fraction in heart failure patients with preserved and reduced ejection fraction. Circ Heart Fail 5:720–726. CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Dutta P, Nahrendorf M (2015) Monocytes in myocardial infarction. Arterioscler Thromb Vasc Biol 35:1066–1070. CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Epelman S, Lavine KJ, Beaudin AE, Sojka DK, Carrero JA, Calderon B, Brija T, Gautier EL, Ivanov S, Satpathy AT, Schilling JD, Schwendener R, Sergin I, Razani B, Forsberg EC, Yokoyama WM, Unanue ER, Colonna M, Randolph GJ, Mann DL (2014) Embryonic and adult-derived resident cardiac macrophages are maintained through distinct mechanisms at steady state and during inflammation. Immunity 40:91–104. CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Fabre A, Sheppard MN (2006) Sudden adult death syndrome and other non-ischaemic causes of sudden cardiac death. Heart 92:316–320. CrossRefPubMedGoogle Scholar
  51. 51.
    Fairweather D, Rose NR (2007) Coxsackievirus-induced myocarditis in mice: a model of autoimmune disease for studying immunotoxicity. Methods 41:118–122. CrossRefPubMedPubMedCentralGoogle Scholar
  52. 52.
    Fan D, Takawale A, Lee J, Kassiri Z (2012) Cardiac fibroblasts, fibrosis and extracellular matrix remodeling in heart disease. Fibrogenes Tissue Repair 5:15. CrossRefGoogle Scholar
  53. 53.
    Fernandez-Aviles F (2018) Cardiac regeneration in 2017: novel paradigms in the fight against heart failure. Nat Rev Cardiol 15:73–74. CrossRefPubMedGoogle Scholar
  54. 54.
    Ferrari R, Bueno H, Chioncel O, Cleland JG, Stough WG, Lettino M, Metra M, Parissis JT, Pinto F, Ponikowski P, Ruschitzka F, Tavazzi L (2018) Acute heart failure: lessons learned, roads ahead. Eur J Heart Fail 20:842–850. CrossRefPubMedGoogle Scholar
  55. 55.
    Fomovsky GM, Rouillard AD, Holmes JW (2012) Regional mechanics determine collagen fiber structure in healing myocardial infarcts. J Mol Cell Cardiol 52:1083–1090. CrossRefPubMedPubMedCentralGoogle Scholar
  56. 56.
    Frangogiannis NG (2018) Cardiac fibrosis: Cell biological mechanisms, molecular pathways and therapeutic opportunities. Mol Aspects Med. CrossRefPubMedGoogle Scholar
  57. 57.
    Frangogiannis NG (2018) Cell biological mechanisms in regulation of the post-infarction inflammatory response. Curr Opin Physiol 1:7–13. CrossRefPubMedGoogle Scholar
  58. 58.
    Frangogiannis NG (2017) The extracellular matrix in myocardial injury, repair, and remodeling. J Clin Invest 127:1600–1612. CrossRefPubMedPubMedCentralGoogle Scholar
  59. 59.
    Frangogiannis NG (2016) The functional pluralism of fibroblasts in the infarcted myocardium. Circ Res 119:1049–1051. CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Frangogiannis NG (2008) The immune system and cardiac repair. Pharmacol Res 58:88–111. CrossRefPubMedPubMedCentralGoogle Scholar
  61. 61.
    Frangogiannis NG (2012) Regulation of the inflammatory response in cardiac repair. Circ Res 110:159–173. CrossRefPubMedPubMedCentralGoogle Scholar
  62. 62.
    Frangogiannis NG, Lindsey ML, Michael LH, Youker KA, Bressler RB, Mendoza LH, Spengler RN, Smith CW, Entman ML (1998) Resident cardiac mast cells degranulate and release preformed TNF-alpha, initiating the cytokine cascade in experimental canine myocardial ischemia/reperfusion. Circulation 98:699–710. CrossRefPubMedGoogle Scholar
  63. 63.
    Frangogiannis NG, Mendoza LH, Ren G, Akrivakis S, Jackson PL, Michael LH, Smith CW, Entman ML (2003) MCSF expression is induced in healing myocardial infarcts and may regulate monocyte and endothelial cell phenotype. Am J Physiol Heart Circ Physiol 285:H483–H492. CrossRefPubMedGoogle Scholar
  64. 64.
    Frangogiannis NG, Ren G, Dewald O, Zymek P, Haudek S, Koerting A, Winkelmann K, Michael LH, Lawler J, Entman ML (2005) Critical role of endogenous thrombospondin-1 in preventing expansion of healing myocardial infarcts. Circulation 111:2935–2942. CrossRefPubMedGoogle Scholar
  65. 65.
    Freichel M, Berlin M, Schurger A, Mathar I, Bacmeister L, Medert R, Frede W, Marx A, Segin S, Londono JEC (2017) TRP channels in the heart. In: Emir TLR (ed) Neurobiology of TRP channels. CRC, Boca Rato, pp 149–185CrossRefGoogle Scholar
  66. 66.
    Fung G, Luo H, Qiu Y, Yang D, McManus B (2016) Myocarditis. Circ Res 118:496–514. CrossRefPubMedGoogle Scholar
  67. 67.
    Fuse K, Chan G, Liu Y, Gudgeon P, Husain M, Chen M, Yeh WC, Akira S, Liu PP (2005) Myeloid differentiation factor-88 plays a crucial role in the pathogenesis of Coxsackievirus B3-induced myocarditis and influences type I interferon production. Circulation 112:2276–2285. CrossRefPubMedGoogle Scholar
  68. 68.
    Gabbiani G (2003) The myofibroblast in wound healing and fibrocontractive diseases. J Pathol 200:500–503. CrossRefPubMedGoogle Scholar
  69. 69.
    Gaggar A, Jackson PL, Noerager BD, O’Reilly PJ, McQuaid DB, Rowe SM, Clancy JP, Blalock JE (2008) A novel proteolytic cascade generates an extracellular matrix-derived chemoattractant in chronic neutrophilic inflammation. J Immunol 180:5662–5669. CrossRefPubMedPubMedCentralGoogle Scholar
  70. 70.
    Gao XM, Dart AM, Dewar E, Jennings G, Du XJ (2000) Serial echocardiographic assessment of left ventricular dimensions and function after myocardial infarction in mice. Cardiovasc Res 45:330–338. CrossRefPubMedGoogle Scholar
  71. 71.
    Garcia-Menendez L, Karamanlidis G, Kolwicz S, Tian R (2013) Substrain specific response to cardiac pressure overload in C57BL/6 mice. Am J Physiol Heart Circ Physiol 305:H397–H402. CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Garlie JB, Hamid T, Gu Y, Ismahil MA, Chandrasekar B, Prabhu SD (2011) Tumor necrosis factor receptor 2 signaling limits beta-adrenergic receptor-mediated cardiac hypertrophy in vivo. Basic Res Cardiol 106:1193–1205. CrossRefPubMedGoogle Scholar
  73. 73.
    Garmaroudi FS, Marchant D, Hendry R, Luo H, Yang D, Ye X, Shi J, McManus BM (2015) Coxsackievirus B3 replication and pathogenesis. Future Microbiol 10:629–653. CrossRefPubMedGoogle Scholar
  74. 74.
    Geerling JC, Engeland WC, Kawata M, Loewy AD (2006) Aldosterone target neurons in the nucleus tractus solitarius drive sodium appetite. J Neurosci 26:411–417. CrossRefPubMedPubMedCentralGoogle Scholar
  75. 75.
    Gehrmann J, Frantz S, Maguire CT, Vargas M, Ducharme A, Wakimoto H, Lee RT, Berul CI (2001) Electrophysiological characterization of murine myocardial ischemia and infarction. Basic Res Cardiol 96:237–250. CrossRefPubMedGoogle Scholar
  76. 76.
    Gharacholou SM, Alexander KP, Chen AY, Wang TY, Melloni C, Gibler WB, Pollack CV Jr, Ohman EM, Peterson ED, Roe MT (2010) Implications and reasons for the lack of use of reperfusion therapy in patients with ST-segment elevation myocardial infarction: findings from the CRUSADE initiative. Am Heart J 159:757–763. CrossRefGoogle Scholar
  77. 77.
    Gill SE, Parks WC (2008) Metalloproteinases and their inhibitors: regulators of wound healing. Int J Biochem Cell Biol 40:1334–1347. CrossRefPubMedGoogle Scholar
  78. 78.
    Gomolak JR, Didion SP (2014) Angiotensin II-induced endothelial dysfunction is temporally linked with increases in interleukin-6 and vascular macrophage accumulation. Front Physiol 5:396. CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Gonzalez GE, Rhaleb NE, D’Ambrosio MA, Nakagawa P, Liu Y, Leung P, Dai X, Yang XP, Peterson EL, Carretero OA (2015) Deletion of interleukin-6 prevents cardiac inflammation, fibrosis and dysfunction without affecting blood pressure in angiotensin II-high salt-induced hypertension. J Hypertens 33:144–152. CrossRefPubMedPubMedCentralGoogle Scholar
  80. 80.
    Gordon JW, Shaw JA, Kirshenbaum LA (2011) Multiple facets of NF-kappaB in the heart: to be or not to NF-kappaB. Circ Res 108:1122–1132. CrossRefPubMedGoogle Scholar
  81. 81.
    Grisanti LA, Gumpert AM, Traynham CJ, Gorsky JE, Repas AA, Gao E, Carter RL, Yu D, Calvert JW, Garcia AP, Ibanez B, Rabinowitz JE, Koch WJ, Tilley DG (2016) Leukocyte-expressed beta2-adrenergic receptors are essential for survival after acute myocardial injury. Circulation 134:153–167. CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Grisanti LA, Traynham CJ, Repas AA, Gao E, Koch WJ, Tilley DG (2016) beta2-Adrenergic receptor-dependent chemokine receptor 2 expression regulates leukocyte recruitment to the heart following acute injury. Proc Natl Acad Sci USA 113:15126–15131. CrossRefPubMedGoogle Scholar
  83. 83.
    Gurantz D, Cowling RT, Varki N, Frikovsky E, Moore CD, Greenberg BH (2005) IL-1beta and TNF-alpha upregulate angiotensin II type 1 (AT1) receptors on cardiac fibroblasts and are associated with increased AT1 density in the post-MI heart. J Mol Cell Cardiol 38:505–515. CrossRefPubMedGoogle Scholar
  84. 84.
    Guyenet PG (2006) The sympathetic control of blood pressure. Nat Rev Neurosci 7:335–346. CrossRefPubMedGoogle Scholar
  85. 85.
    Guzik TJ, Hoch NE, Brown KA, McCann LA, Rahman A, Dikalov S, Goronzy J, Weyand C, Harrison DG (2007) Role of the T cell in the genesis of angiotensin II induced hypertension and vascular dysfunction. J Exp Med 204:2449–2460. CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Hanif W, Alex L, Su Y, Shinde AV, Russo I, Li N, Frangogiannis NG (2017) Left atrial remodeling, hypertrophy, and fibrosis in mouse models of heart failure. Cardiovasc Pathol 30:27–37. CrossRefPubMedPubMedCentralGoogle Scholar
  87. 87.
    Haudek SB, Cheng J, Du J, Wang Y, Hermosillo-Rodriguez J, Trial J, Taffet GE, Entman ML (2010) Monocytic fibroblast precursors mediate fibrosis in angiotensin-II-induced cardiac hypertrophy. J Mol Cell Cardiol 49:499–507. CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Hausenloy DJ, Yellon DM (2013) Myocardial ischemia-reperfusion injury: a neglected therapeutic target. J Clin Invest 123:92–100. CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    He L, Kim T, Long Q, Liu J, Wang P, Zhou Y, Ding Y, Prasain J, Wood PA, Yang Q (2012) Carnitine palmitoyltransferase-1b deficiency aggravates pressure overload-induced cardiac hypertrophy caused by lipotoxicity. Circulation 126:1705–1716. CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Hermans H, Swinnen M, Pokreisz P, Caluwe E, Dymarkowski S, Herregods MC, Janssens S (1985) Herijgers P (2014) Murine pressure overload models: a 30-MHz look brings a whole new “sound” into data interpretation. J Appl Physiol 117:563–571. CrossRefGoogle Scholar
  91. 91.
    Hermida N, Michel L, Esfahani H, Dubois-Deruy E, Hammond J, Bouzin C, Markl A, Colin H, Steenbergen AV, De Meester C, Beauloye C, Horman S, Yin X, Mayr M, Balligand JL (2018) Cardiac myocyte beta3-adrenergic receptors prevent myocardial fibrosis by modulating oxidant stress-dependent paracrine signaling. Eur Heart J 39:888–898. CrossRefPubMedGoogle Scholar
  92. 92.
    Heusch G, Gersh BJ (2017) The pathophysiology of acute myocardial infarction and strategies of protection beyond reperfusion: a continual challenge. Eur Heart J 38:774–784. CrossRefPubMedGoogle Scholar
  93. 93.
    Heusch G, Libby P, Gersh B, Yellon D, Bohm M, Lopaschuk G, Opie L (2014) Cardiovascular remodelling in coronary artery disease and heart failure. Lancet 383:1933–1943. CrossRefPubMedPubMedCentralGoogle Scholar
  94. 94.
    Hinrichs S, Scherschel K, Kruger S, Neumann JT, Schwarzl M, Yan I, Warnke S, Ojeda FM, Zeller T, Karakas M, Keller T, Meyer C, Blankenberg S, Westermann D, Lindner D (2018) Precursor proadrenomedullin influences cardiomyocyte survival and local inflammation related to myocardial infarction. Proc Natl Acad Sci USA 115:E8727–E8736. CrossRefPubMedGoogle Scholar
  95. 95.
    Hinz B (2010) The myofibroblast: paradigm for a mechanically active cell. J Biomech 43:146–155. CrossRefGoogle Scholar
  96. 96.
    Hinz B, Mastrangelo D, Iselin CE, Chaponnier C, Gabbiani G (2001) Mechanical tension controls granulation tissue contractile activity and myofibroblast differentiation. Am J Pathol 159:1009–1020. CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Hinz B, Phan SH, Thannickal VJ, Galli A, Bochaton-Piallat ML, Gabbiani G (2007) The myofibroblast: one function, multiple origins. Am J Pathol 170:1807–1816. CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Ho JE, Enserro D, Brouwers FP, Kizer JR, Shah SJ, Psaty BM, Bartz TM, Santhanakrishnan R, Lee DS, Chan C, Liu K, Blaha MJ, Hillege HL, van der Harst P, van Gilst WH, Kop WJ, Gansevoort RT, Vasan RS, Gardin JM, Levy D, Gottdiener JS, de Boer RA, Larson MG (2016) Predicting Heart Failure With Preserved and Reduced Ejection Fraction: The International Collaboration on Heart Failure Subtypes. Circ Heart Fail. CrossRefPubMedPubMedCentralGoogle Scholar
  99. 99.
    Hofmann U, Frantz S (2015) Role of lymphocytes in myocardial injury, healing, and remodeling after myocardial infarction. Circ Res 116:354–367. CrossRefPubMedGoogle Scholar
  100. 100.
    Horckmans M, Ring L, Duchene J, Santovito D, Schloss MJ, Drechsler M, Weber C, Soehnlein O, Steffens S (2017) Neutrophils orchestrate post-myocardial infarction healing by polarizing macrophages towards a reparative phenotype. Eur Heart J 38:187–197. CrossRefPubMedGoogle Scholar
  101. 101.
    Houde M, Schwertani A, Touil H, Desbiens L, Sarrhini O, Lecomte R, Lepage M, Gagnon H, Takai S, Pejler G, Jacques D, Gobeil F Jr, Day R, D’Orleans-Juste P (2018) Mouse mast cell protease 4 deletion protects heart function and survival after permanent myocardial infarction. Front Pharmacol 9:868. CrossRefPubMedPubMedCentralGoogle Scholar
  102. 102.
    Howangyin KY, Zlatanova I, Pinto C, Ngkelo A, Cochain C, Rouanet M, Vilar J, Lemitre M, Stockmann C, Fleischmann BK, Mallat Z, Silvestre JS (2016) Myeloid-epithelial-reproductive receptor tyrosine kinase and milk fat globule epidermal growth factor 8 coordinately improve remodeling after myocardial infarction via local delivery of vascular endothelial growth factor. Circulation 133:826–839. CrossRefPubMedPubMedCentralGoogle Scholar
  103. 103.
    Huang CH, Vallejo JG, Kollias G, Mann DL (2009) Role of the innate immune system in acute viral myocarditis. Basic Res Cardiol 104:228–237. CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Huang Y, Wright CD, Merkwan CL, Baye NL, Liang Q, Simpson PC, O’Connell TD (2007) An alpha1A-adrenergic-extracellular signal-regulated kinase survival signaling pathway in cardiac myocytes. Circulation 115:763–772. CrossRefPubMedGoogle Scholar
  105. 105.
    Huber SA, Sartini D (2005) Roles of tumor necrosis factor alpha (TNF-alpha) and the p55 TNF receptor in CD1d induction and coxsackievirus B3-induced myocarditis. J Virol 79:2659–2665. CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Huebener P, Abou-Khamis T, Zymek P, Bujak M, Ying X, Chatila K, Haudek S, Thakker G, Frangogiannis NG (2008) CD44 is critically involved in infarct healing by regulating the inflammatory and fibrotic response. J Immunol 180:2625–2633. CrossRefPubMedGoogle Scholar
  107. 107.
    Hufnagel G, Chapman N, Tracy S (1995) A non-cardiovirulent strain of coxsackievirus B3 causes myocarditis in mice with severe combined immunodeficiency syndrome. Eur Heart J 16(Suppl O):18–19. CrossRefPubMedGoogle Scholar
  108. 108.
    Huynh ML, Fadok VA, Henson PM (2002) Phosphatidylserine-dependent ingestion of apoptotic cells promotes TGF-beta1 secretion and the resolution of inflammation. J Clin Invest 109:41–50. CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Ibanez B, Heusch G, Ovize M, Van de Werf F (2015) Evolving therapies for myocardial ischemia/reperfusion injury. J Am Coll Cardiol 65:1454–1471. CrossRefPubMedGoogle Scholar
  110. 110.
    Ibanez B, James S, Agewall S, Antunes MJ, Bucciarelli-Ducci C, Bueno H, Caforio ALP, Crea F, Goudevenos JA, Halvorsen S, Hindricks G, Kastrati A, Lenzen MJ, Prescott E, Roffi M, Valgimigli M, Varenhorst C, Vranckx P, Widimsky P, Group ESCSD (2018) 2017 ESC Guidelines for the management of acute myocardial infarction in patients presenting with ST-segment elevation: The Task Force for the management of acute myocardial infarction in patients presenting with ST-segment elevation of the European Society of Cardiology (ESC). Eur Heart J 39:119–177. CrossRefPubMedGoogle Scholar
  111. 111.
    Ikeuchi M, Tsutsui H, Shiomi T, Matsusaka H, Matsushima S, Wen J, Kubota T, Takeshita A (2004) Inhibition of TGF-beta signaling exacerbates early cardiac dysfunction but prevents late remodeling after infarction. Cardiovasc Res 64:526–535. CrossRefPubMedGoogle Scholar
  112. 112.
    Imai Y, Kariya T, Iwakiri M, Yamada Y, Takimoto E (2018) Sildenafil ameliorates right ventricular early molecular derangement during left ventricular pressure overload. PLoS One 13:e0195528. CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Iwanaga Y, Aoyama T, Kihara Y, Onozawa Y, Yoneda T, Sasayama S (2002) Excessive activation of matrix metalloproteinases coincides with left ventricular remodeling during transition from hypertrophy to heart failure in hypertensive rats. J Am Coll Cardiol 39:1384–1391. CrossRefPubMedGoogle Scholar
  114. 114.
    Iyer RP, de Castro Bras LE, Cannon PL, Ma Y, DeLeon-Pennell KY, Jung M, Flynn ER, Henry JB, Bratton DR, White JA, Fulton LK, Grady AW, Lindsey ML (2016) Defining the sham environment for post-myocardial infarction studies in mice. Am J Physiol Heart Circ Physiol 311:H822–H836. CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Jakel S, Kuckelkorn U, Szalay G, Plotz M, Textoris-Taube K, Opitz E, Klingel K, Stevanovic S, Kandolf R, Kotsch K, Stangl K, Kloetzel PM, Voigt A (2009) Differential interferon responses enhance viral epitope generation by myocardial immunoproteasomes in murine enterovirus myocarditis. Am J Pathol 175:510–518. CrossRefPubMedPubMedCentralGoogle Scholar
  116. 116.
    Janicki JS, Brower GL (2002) The role of myocardial fibrillar collagen in ventricular remodeling and function. J Card Fail 8:S319–S325. CrossRefPubMedGoogle Scholar
  117. 117.
    Jaquenod De Giusti C, Ure AE, Rivadeneyra L, Schattner M, Gomez RM (2015) Macrophages and galectin 3 play critical roles in CVB3-induced murine acute myocarditis and chronic fibrosis. J Mol Cell Cardiol 85:58–70. CrossRefPubMedGoogle Scholar
  118. 118.
    Jeong EM, Monasky MM, Gu L, Taglieri DM, Patel BG, Liu H, Wang Q, Greener I, Dudley SC Jr, Solaro RJ (2013) Tetrahydrobiopterin improves diastolic dysfunction by reversing changes in myofilament properties. J Mol Cell Cardiol 56:44–54. CrossRefPubMedGoogle Scholar
  119. 119.
    Joiner ML, Koval OM, Li J, He BJ, Allamargot C, Gao Z, Luczak ED, Hall DD, Fink BD, Chen B, Yang J, Moore SA, Scholz TD, Strack S, Mohler PJ, Sivitz WI, Song LS, Anderson ME (2012) CaMKII determines mitochondrial stress responses in heart. Nature 491:269–273. CrossRefPubMedPubMedCentralGoogle Scholar
  120. 120.
    Jong WM, Ten Cate H, Linnenbank AC, de Boer OJ, Reitsma PH, de Winter RJ, Zuurbier CJ (2016) Reduced acute myocardial ischemia-reperfusion injury in IL-6-deficient mice employing a closed-chest model. Inflamm Res 65:489–499. CrossRefPubMedPubMedCentralGoogle Scholar
  121. 121.
    Jugdutt BI (2010) Preventing adverse remodeling and rupture during healing after myocardial infarction in mice and humans. Circulation 122:103–105. CrossRefPubMedGoogle Scholar
  122. 122.
    Kallikourdis M, Martini E, Carullo P, Sardi C, Roselli G, Greco CM, Vignali D, Riva F, Ormbostad Berre AM, Stolen TO, Fumero A, Faggian G, Di Pasquale E, Elia L, Rumio C, Catalucci D, Papait R, Condorelli G (2017) T cell costimulation blockade blunts pressure overload-induced heart failure. Nat Commun 8:14680. CrossRefPubMedPubMedCentralGoogle Scholar
  123. 123.
    Kandolf R, Hofschneider PH (1985) Molecular cloning of the genome of a cardiotropic Coxsackie B3 virus: full-length reverse-transcribed recombinant cDNA generates infectious virus in mammalian cells. Proc Natl Acad Sci USA 82:4818–4822. CrossRefPubMedGoogle Scholar
  124. 124.
    Kato H, Takeuchi O, Sato S, Yoneyama M, Yamamoto M, Matsui K, Uematsu S, Jung A, Kawai T, Ishii KJ, Yamaguchi O, Otsu K, Tsujimura T, Koh CS, Reis e Sousa C, Matsuura Y, Fujita T, Akira S (2006) Differential roles of MDA5 and RIG-I helicases in the recognition of RNA viruses. Nature 441:101–105. CrossRefPubMedGoogle Scholar
  125. 125.
    Kazakov A, Hall RA, Werner C, Meier T, Trouvain A, Rodionycheva S, Nickel A, Lammert F, Maack C, Bohm M, Laufs U (2018) Raf kinase inhibitor protein mediates myocardial fibrosis under conditions of enhanced myocardial oxidative stress. Basic Res Cardiol 113:42. CrossRefPubMedPubMedCentralGoogle Scholar
  126. 126.
    Kemp CD, Conte JV (2012) The pathophysiology of heart failure. Cardiovasc Pathol 21:365–371. CrossRefPubMedGoogle Scholar
  127. 127.
    Kinet JP (2007) The essential role of mast cells in orchestrating inflammation. Immunol Rev 217:5–7. CrossRefPubMedGoogle Scholar
  128. 128.
    Kishimoto C, Kuribayashi K, Masuda T, Tomioka N, Kawai C (1985) Immunologic behavior of lymphocytes in experimental viral myocarditis: significance of T lymphocytes in the severity of myocarditis and silent myocarditis in BALB/c-nu/nu mice. Circulation 71:1247–1254. CrossRefPubMedGoogle Scholar
  129. 129.
    Klingel K, Hohenadl C, Canu A, Albrecht M, Seemann M, Mall G, Kandolf R (1992) Ongoing enterovirus-induced myocarditis is associated with persistent heart muscle infection: quantitative analysis of virus replication, tissue damage, and inflammation. Proc Natl Acad Sci USA 89:314–318. CrossRefPubMedGoogle Scholar
  130. 130.
    Klocke R, Tian W, Kuhlmann MT, Nikol S (2007) Surgical animal models of heart failure related to coronary heart disease. Cardiovasc Res 74:29–38. CrossRefPubMedGoogle Scholar
  131. 131.
    Knight WE, Chen S, Zhang Y, Oikawa M, Wu M, Zhou Q, Miller CL, Cai Y, Mickelsen DM, Moravec C, Small EM, Abe J, Yan C (2016) PDE1C deficiency antagonizes pathological cardiac remodeling and dysfunction. Proc Natl Acad Sci USA 113:E7116–E7125. CrossRefPubMedGoogle Scholar
  132. 132.
    Koitabashi N, Danner T, Zaiman AL, Pinto YM, Rowell J, Mankowski J, Zhang D, Nakamura T, Takimoto E, Kass DA (2011) Pivotal role of cardiomyocyte TGF-beta signaling in the murine pathological response to sustained pressure overload. J Clin Invest 121:2301–2312. CrossRefPubMedPubMedCentralGoogle Scholar
  133. 133.
    Kong P, Christia P, Frangogiannis NG (2014) The pathogenesis of cardiac fibrosis. Cell Mol Life Sci 71:549–574. CrossRefPubMedGoogle Scholar
  134. 134.
    Kong P, Shinde AV, Su Y, Russo I, Chen B, Saxena A, Conway SJ, Graff JM, Frangogiannis NG (2018) Opposing actions of fibroblast and cardiomyocyte Smad3 signaling in the infarcted myocardium. Circulation 137:707–724. CrossRefPubMedGoogle Scholar
  135. 135.
    Kraft L, Erdenesukh T, Sauter M, Tschope C, Klingel K (2019) Blocking the IL-1beta signalling pathway prevents chronic viral myocarditis and cardiac remodeling. Basic Res Cardiol 114:11. CrossRefPubMedGoogle Scholar
  136. 136.
    Krysko DV, Agostinis P, Krysko O, Garg AD, Bachert C, Lambrecht BN, Vandenabeele P (2011) Emerging role of damage-associated molecular patterns derived from mitochondria in inflammation. Trends Immunol 32:157–164. CrossRefPubMedGoogle Scholar
  137. 137.
    Kubota T, Bounoutas GS, Miyagishima M, Kadokami T, Sanders VJ, Bruton C, Robbins PD, McTiernan CF, Feldman AM (2000) Soluble tumor necrosis factor receptor abrogates myocardial inflammation but not hypertrophy in cytokine-induced cardiomyopathy. Circulation 101:2518–2525. CrossRefPubMedGoogle Scholar
  138. 138.
    Kumar AG, Ballantyne CM, Michael LH, Kukielka GL, Youker KA, Lindsey ML, Hawkins HK, Birdsall HH, MacKay CR, LaRosa GJ, Rossen RD, Smith CW, Entman ML (1997) Induction of monocyte chemoattractant protein-1 in the small veins of the ischemic and reperfused canine myocardium. Circulation 95:693–700. CrossRefPubMedGoogle Scholar
  139. 139.
    Kurisu S, Ozono R, Oshima T, Kambe M, Ishida T, Sugino H, Matsuura H, Chayama K, Teranishi Y, Iba O, Amano K, Matsubara H (2003) Cardiac angiotensin II type 2 receptor activates the kinin/NO system and inhibits fibrosis. Hypertension 41:99–107. CrossRefPubMedGoogle Scholar
  140. 140.
    Kzhyshkowska J, Workman G, Cardo-Vila M, Arap W, Pasqualini R, Gratchev A, Krusell L, Goerdt S, Sage EH (2006) Novel function of alternatively activated macrophages: stabilin-1-mediated clearance of SPARC. J Immunol 176:5825–5832. CrossRefPubMedGoogle Scholar
  141. 141.
    Lang C, Sauter M, Szalay G, Racchi G, Grassi G, Rainaldi G, Mercatanti A, Lang F, Kandolf R, Klingel K (2008) Connective tissue growth factor: a crucial cytokine-mediating cardiac fibrosis in ongoing enterovirus myocarditis. J Mol Med (Berl) 86:49–60. CrossRefGoogle Scholar
  142. 142.
    Laroumanie F, Douin-Echinard V, Pozzo J, Lairez O, Tortosa F, Vinel C, Delage C, Calise D, Dutaur M, Parini A, Pizzinat N (2014) CD4 + T cells promote the transition from hypertrophy to heart failure during chronic pressure overload. Circulation 129:2111–2124. CrossRefPubMedGoogle Scholar
  143. 143.
    Leask A (2015) Getting to the heart of the matter: new insights into cardiac fibrosis. Circ Res 116:1269–1276. CrossRefPubMedGoogle Scholar
  144. 144.
    Leuschner F, Dutta P, Gorbatov R, Novobrantseva TI, Donahoe JS, Courties G, Lee KM, Kim JI, Markmann JF, Marinelli B, Panizzi P, Lee WW, Iwamoto Y, Milstein S, Epstein-Barash H, Cantley W, Wong J, Cortez-Retamozo V, Newton A, Love K, Libby P, Pittet MJ, Swirski FK, Koteliansky V, Langer R, Weissleder R, Anderson DG, Nahrendorf M (2011) Therapeutic siRNA silencing in inflammatory monocytes in mice. Nat Biotechnol 29:1005–1010. CrossRefPubMedPubMedCentralGoogle Scholar
  145. 145.
    Levick SP, Melendez GC, Plante E, McLarty JL, Brower GL, Janicki JS (2011) Cardiac mast cells: the centrepiece in adverse myocardial remodelling. Cardiovasc Res 89:12–19. CrossRefPubMedGoogle Scholar
  146. 146.
    Li J, Brown LF, Hibberd MG, Grossman JD, Morgan JP, Simons M (1996) VEGF, flk-1, and flt-1 expression in a rat myocardial infarction model of angiogenesis. Am J Physiol 270:H1803–H1811. CrossRefPubMedGoogle Scholar
  147. 147.
    Li L, Guo X, Chen Y, Yin H, Li J, Doan J, Liu Q (2016) Assessment of cardiac morphological and functional changes in mouse model of transverse aortic constriction by echocardiographic imaging. J Vis Exp. CrossRefPubMedPubMedCentralGoogle Scholar
  148. 148.
    Liao Y, Takashima S, Maeda N, Ouchi N, Komamura K, Shimomura I, Hori M, Matsuzawa Y, Funahashi T, Kitakaze M (2005) Exacerbation of heart failure in adiponectin-deficient mice due to impaired regulation of AMPK and glucose metabolism. Cardiovasc Res 67:705–713. CrossRefPubMedGoogle Scholar
  149. 149.
    Lim BK, Choe SC, Shin JO, Ho SH, Kim JM, Yu SS, Kim S, Jeon ES (2002) Local expression of interleukin-1 receptor antagonist by plasmid DNA improves mortality and decreases myocardial inflammation in experimental coxsackieviral myocarditis. Circulation 105:1278–1281. CrossRefPubMedGoogle Scholar
  150. 150.
    Lindner D, Hilbrandt M, Marggraf K, Becher PM, Hilfiker-Kleiner D, Klingel K, Pauschinger M, Schultheiss HP, Tschope C, Westermann D (2012) Protective function of STAT3 in CVB3-induced myocarditis. Cardiol Res Pract 2012:437623. CrossRefPubMedPubMedCentralGoogle Scholar
  151. 151.
    Lindner D, Li J, Savvatis K, Klingel K, Blankenberg S, Tschope C, Westermann D (2014) Cardiac fibroblasts aggravate viral myocarditis: cell specific coxsackievirus B3 replication. Mediat Inflamm 2014:519528. CrossRefGoogle Scholar
  152. 152.
    Lindner D, Westermann D (2015) Firefighting in viral myocarditis—extinguish galectin-3 to control the inflamed heart? J Mol Cell Cardiol 85:226–228. CrossRefPubMedGoogle Scholar
  153. 153.
    Lindner D, Zietsch C, Tank J, Sossalla S, Fluschnik N, Hinrichs S, Maier L, Poller W, Blankenberg S, Schultheiss HP, Tschope C, Westermann D (2014) Cardiac fibroblasts support cardiac inflammation in heart failure. Basic Res Cardiol 109:428. CrossRefPubMedGoogle Scholar
  154. 154.
    Lindsey ML (2018) Assigning matrix metalloproteinase roles in ischaemic cardiac remodelling. Nat Rev Cardiol 15:471–479. CrossRefPubMedPubMedCentralGoogle Scholar
  155. 155.
    Lindsey ML, Bolli R, Canty JM Jr, Du XJ, Frangogiannis NG, Frantz S, Gourdie RG, Holmes JW, Jones SP, Kloner RA, Lefer DJ, Liao R, Murphy E, Ping P, Przyklenk K, Recchia FA, Schwartz Longacre L, Ripplinger CM, Van Eyk JE, Heusch G (2018) Guidelines for experimental models of myocardial ischemia and infarction. Am J Physiol Heart Circ Physiol 314:H812–H838. CrossRefPubMedPubMedCentralGoogle Scholar
  156. 156.
    Lindsey ML, Jung M, Yabluchanskiy A, Cannon PL, Iyer RP, Flynn ER, DeLeon-Pennell KY, Valerio FM, Harrison CL, Ripplinger CM, Hall ME, Ma Y (2019) Exogenous CXCL4 infusion inhibits macrophage phagocytosis by limiting CD36 signalling to enhance post-myocardial infarction cardiac dilation and mortality. Cardiovasc Res 115:395–408. CrossRefPubMedGoogle Scholar
  157. 157.
    Lindsey ML, Kassiri Z, Virag JAI, de Castro Bras LE, Scherrer-Crosbie M (2018) Guidelines for measuring cardiac physiology in mice. Am J Physiol Heart Circ Physiol 314:H733–H752. CrossRefPubMedPubMedCentralGoogle Scholar
  158. 158.
    Lipps C, Nguyen JH, Pyttel L, Lynch TLT, Liebetrau C, Aleshcheva G, Voss S, Dorr O, Nef HM, Mollmann H, Hamm CW, Sadayappan S, Troidl C (2016) N-terminal fragment of cardiac myosin binding protein-C triggers pro-inflammatory responses in vitro. J Mol Cell Cardiol 99:47–56. CrossRefPubMedPubMedCentralGoogle Scholar
  159. 159.
    Lopez B, Querejeta R, Gonzalez A, Larman M, Diez J (2012) Collagen cross-linking but not collagen amount associates with elevated filling pressures in hypertensive patients with stage C heart failure: potential role of lysyl oxidase. Hypertension 60:677–683. CrossRefPubMedGoogle Scholar
  160. 160.
    Lother A, Berger S, Gilsbach R, Rosner S, Ecke A, Barreto F, Bauersachs J, Schutz G, Hein L (2011) Ablation of mineralocorticoid receptors in myocytes but not in fibroblasts preserves cardiac function. Hypertension 57:746–754. CrossRefPubMedGoogle Scholar
  161. 161.
    Lother A, Furst D, Bergemann S, Gilsbach R, Grahammer F, Huber TB, Hilgendorf I, Bode C, Moser M, Hein L (2016) Deoxycorticosterone acetate/salt-induced cardiac but not renal injury is mediated by endothelial mineralocorticoid receptors independently from blood pressure. Hypertension 67:130–138. CrossRefPubMedGoogle Scholar
  162. 162.
    Lovelock JD, Monasky MM, Jeong EM, Lardin HA, Liu H, Patel BG, Taglieri DM, Gu L, Kumar P, Pokhrel N, Zeng D, Belardinelli L, Sorescu D, Solaro RJ, Dudley SC Jr (2012) Ranolazine improves cardiac diastolic dysfunction through modulation of myofilament calcium sensitivity. Circ Res 110:841–850. CrossRefPubMedPubMedCentralGoogle Scholar
  163. 163.
    Lutgens E, Daemen MJ, de Muinck ED, Debets J, Leenders P, Smits JF (1999) Chronic myocardial infarction in the mouse: cardiac structural and functional changes. Cardiovasc Res 41:586–593. CrossRefPubMedGoogle Scholar
  164. 164.
    Lymperopoulos A, Rengo G, Koch WJ (2013) Adrenergic nervous system in heart failure: pathophysiology and therapy. Circ Res 113:739–753. CrossRefPubMedGoogle Scholar
  165. 165.
    Lyons RM, Keski-Oja J, Moses HL (1988) Proteolytic activation of latent transforming growth factor-beta from fibroblast-conditioned medium. J Cell Biol 106:1659–1665. CrossRefPubMedGoogle Scholar
  166. 166.
    Ma J, Luo T, Zeng Z, Fu H, Asano Y, Liao Y, Minamino T, Kitakaze M (2016) Histone deacetylase inhibitor phenylbutyrate exaggerates heart failure in pressure overloaded mice independently of HDAC inhibition. Sci Rep 6:34036. CrossRefPubMedPubMedCentralGoogle Scholar
  167. 167.
    Ma Y, Yabluchanskiy A, Iyer RP, Cannon PL, Flynn ER, Jung M, Henry J, Cates CA, Deleon-Pennell KY, Lindsey ML (2016) Temporal neutrophil polarization following myocardial infarction. Cardiovasc Res 110:51–61. CrossRefPubMedPubMedCentralGoogle Scholar
  168. 168.
    Mann DL (2011) The emerging role of innate immunity in the heart and vascular system: for whom the cell tolls. Circ Res 108:1133–1145. CrossRefPubMedPubMedCentralGoogle Scholar
  169. 169.
    Mann DL, Bristow MR (2005) Mechanisms and models in heart failure: the biomechanical model and beyond. Circulation 111:2837–2849. CrossRefPubMedGoogle Scholar
  170. 170.
    Marchant DJ, Boyd JH, Lin DC, Granville DJ, Garmaroudi FS, McManus BM (2012) Inflammation in myocardial diseases. Circ Res 110:126–144. CrossRefPubMedGoogle Scholar
  171. 171.
    Martino MM, Briquez PS, Ranga A, Lutolf MP, Hubbell JA (2013) Heparin-binding domain of fibrin(ogen) binds growth factors and promotes tissue repair when incorporated within a synthetic matrix. Proc Natl Acad Sci USA 110:4563–4568. CrossRefPubMedGoogle Scholar
  172. 172.
    Marvar PJ, Thabet SR, Guzik TJ, Lob HE, McCann LA, Weyand C, Gordon FJ, Harrison DG (2010) Central and peripheral mechanisms of T-lymphocyte activation and vascular inflammation produced by angiotensin II-induced hypertension. Circ Res 107:263–270. CrossRefPubMedPubMedCentralGoogle Scholar
  173. 173.
    McEwan PE, Gray GA, Sherry L, Webb DJ, Kenyon CJ (1998) Differential effects of angiotensin II on cardiac cell proliferation and intramyocardial perivascular fibrosis in vivo. Circulation 98:2765–2773. CrossRefPubMedGoogle Scholar
  174. 174.
    Mehrad B, Keane MP, Strieter RM (2007) Chemokines as mediators of angiogenesis. Thromb Haemost 97:755–762. CrossRefPubMedPubMedCentralGoogle Scholar
  175. 175.
    Melleby AO, Romaine A, Aronsen JM, Veras I, Zhang L, Sjaastad I, Lunde IG, Christensen G (2018) A novel method for high precision aortic constriction that allows for generation of specific cardiac phenotypes in mice. Cardiovasc Res 114:1680–1690. CrossRefPubMedGoogle Scholar
  176. 176.
    Melnick JL (1983) Portraits of viruses: the picornaviruses. Intervirology 20:61–100. CrossRefPubMedGoogle Scholar
  177. 177.
    Meng X, Yang J, Dong M, Zhang K, Tu E, Gao Q, Chen W, Zhang C, Zhang Y (2016) Regulatory T cells in cardiovascular diseases. Nat Rev Cardiol 13:167–179. CrossRefPubMedGoogle Scholar
  178. 178.
    Mersmann J, Habeck K, Latsch K, Zimmermann R, Jacoby C, Fischer JW, Hartmann C, Schrader J, Kirschning CJ, Zacharowski K (2011) Left ventricular dilation in toll-like receptor 2 deficient mice after myocardial ischemia/reperfusion through defective scar formation. Basic Res Cardiol 106:89–98. CrossRefPubMedGoogle Scholar
  179. 179.
    Michael LH, Entman ML, Hartley CJ, Youker KA, Zhu J, Hall SR, Hawkins HK, Berens K, Ballantyne CM (1995) Myocardial ischemia and reperfusion: a murine model. Am J Physiol 269:H2147–H2154. CrossRefPubMedGoogle Scholar
  180. 180.
    Mohammed SF, Ohtani T, Korinek J, Lam CS, Larsen K, Simari RD, Valencik ML, Burnett JC Jr, Redfield MM (2010) Mineralocorticoid accelerates transition to heart failure with preserved ejection fraction via “nongenomic effects”. Circulation 122:370–378. CrossRefPubMedPubMedCentralGoogle Scholar
  181. 181.
    Mohammed SF, Storlie JR, Oehler EA, Bowen LA, Korinek J, Lam CS, Simari RD, Burnett JC Jr, Redfield MM (2012) Variable phenotype in murine transverse aortic constriction. Cardiovasc Pathol 21:188–198. CrossRefPubMedGoogle Scholar
  182. 182.
    Mollenhauer M, Friedrichs K, Lange M, Gesenberg J, Remane L, Kerkenpass C, Krause J, Schneider J, Ravekes T, Maass M, Halbach M, Peinkofer G, Saric T, Mehrkens D, Adam M, Deuschl FG, Lau D, Geertz B, Manchanda K, Eschenhagen T, Kubala L, Rudolph TK, Wu Y, Tang WHW, Hazen SL, Baldus S, Klinke A, Rudolph V (2017) Myeloperoxidase mediates postischemic arrhythmogenic ventricular remodeling. Circ Res 121:56–70. CrossRefPubMedPubMedCentralGoogle Scholar
  183. 183.
    Mollmann H, Nef HM, Kostin S, von Kalle C, Pilz I, Weber M, Schaper J, Hamm CW, Elsasser A (2006) Bone marrow-derived cells contribute to infarct remodelling. Cardiovasc Res 71:661–671. CrossRefPubMedGoogle Scholar
  184. 184.
    Montecucco F, Carbone F, Schindler TH (2016) Pathophysiology of ST-segment elevation myocardial infarction: novel mechanisms and treatments. Eur Heart J 37:1268–1283. CrossRefPubMedGoogle Scholar
  185. 185.
    Moore-Morris T, Guimaraes-Camboa N, Banerjee I, Zambon AC, Kisseleva T, Velayoudon A, Stallcup WB, Gu Y, Dalton ND, Cedenilla M, Gomez-Amaro R, Zhou B, Brenner DA, Peterson KL, Chen J, Evans SM (2014) Resident fibroblast lineages mediate pressure overload-induced cardiac fibrosis. J Clin Invest 124:2921–2934. CrossRefPubMedPubMedCentralGoogle Scholar
  186. 186.
    Moore JBT, Tang XL, Zhao J, Fischer AG, Wu WJ, Uchida S, Gumpert AM, Stowers H, Wysoczynski M, Bolli R (2018) Epigenetically modified cardiac mesenchymal stromal cells limit myocardial fibrosis and promote functional recovery in a model of chronic ischemic cardiomyopathy. Basic Res Cardiol 114:3. CrossRefPubMedGoogle Scholar
  187. 187.
    Mouton AJ, DeLeon-Pennell KY, Rivera Gonzalez OJ, Flynn ER, Freeman TC, Saucerman JJ, Garrett MR, Ma Y, Harmancey R, Lindsey ML (2018) Mapping macrophage polarization over the myocardial infarction time continuum. Basic Res Cardiol 113:26. CrossRefPubMedPubMedCentralGoogle Scholar
  188. 188.
    Muller J, Gorressen S, Grandoch M, Feldmann K, Kretschmer I, Lehr S, Ding Z, Schmitt JP, Schrader J, Garbers C, Heusch G, Kelm M, Scheller J, Fischer JW (2014) Interleukin-6-dependent phenotypic modulation of cardiac fibroblasts after acute myocardial infarction. Basic Res Cardiol 109:440. CrossRefPubMedGoogle Scholar
  189. 189.
    Murdoch CE, Chaubey S, Zeng L, Yu B, Ivetic A, Walker SJ, Vanhoutte D, Heymans S, Grieve DJ, Cave AC, Brewer AC, Zhang M, Shah AM (2014) Endothelial NADPH oxidase-2 promotes interstitial cardiac fibrosis and diastolic dysfunction through proinflammatory effects and endothelial-mesenchymal transition. J Am Coll Cardiol 63:2734–2741. CrossRefPubMedGoogle Scholar
  190. 190.
    Murphy AM, Wong AL, Bezuhly M (2015) Modulation of angiotensin II signaling in the prevention of fibrosis. Fibrogenes Tissue Repair 8:7. CrossRefGoogle Scholar
  191. 191.
    Murray DR, Prabhu SD, Chandrasekar B (2000) Chronic beta-adrenergic stimulation induces myocardial proinflammatory cytokine expression. Circulation 101:2338–2341. CrossRefPubMedGoogle Scholar
  192. 192.
    Nagatomo Y, Carabello BA, Coker ML, McDermott PJ, Nemoto S, Hamawaki M, Spinale FG (2000) Differential effects of pressure or volume overload on myocardial MMP levels and inhibitory control. Am J Physiol Heart Circ Physiol 278:H151–H161. CrossRefPubMedGoogle Scholar
  193. 193.
    Nakaya M, Watari K, Tajima M, Nakaya T, Matsuda S, Ohara H, Nishihara H, Yamaguchi H, Hashimoto A, Nishida M, Nagasaka A, Horii Y, Ono H, Iribe G, Inoue R, Tsuda M, Inoue K, Tanaka A, Kuroda M, Nagata S, Kurose H (2017) Cardiac myofibroblast engulfment of dead cells facilitates recovery after myocardial infarction. J Clin Invest 127:383–401. CrossRefPubMedGoogle Scholar
  194. 194.
    Nathan C, Ding A (2010) Nonresolving inflammation. Cell 140:871–882. CrossRefPubMedGoogle Scholar
  195. 195.
    Neumann FJ, Sousa-Uva M, Ahlsson A, Alfonso F, Banning AP, Benedetto U, Byrne RA, Collet JP, Falk V, Head SJ, Juni P, Kastrati A, Koller A, Kristensen SD, Niebauer J, Richter DJ, Seferovic PM, Sibbing D, Stefanini GG, Windecker S, Yadav R, Zembala MO, Group ESCSD (2019) 2018 ESC/EACTS Guidelines on myocardial revascularization. Eur Heart J 40:87–165. CrossRefPubMedGoogle Scholar
  196. 196.
    Ngkelo A, Richart A, Kirk JA, Bonnin P, Vilar J, Lemitre M, Marck P, Branchereau M, Le Gall S, Renault N, Guerin C, Ranek MJ, Kervadec A, Danelli L, Gautier G, Blank U, Launay P, Camerer E, Bruneval P, Menasche P, Heymes C, Luche E, Casteilla L, Cousin B, Rodewald HR, Kass DA, Silvestre JS (2016) Mast cells regulate myofilament calcium sensitization and heart function after myocardial infarction. J Exp Med 213:1353–1374. CrossRefPubMedPubMedCentralGoogle Scholar
  197. 197.
    Nossuli TO, Lakshminarayanan V, Baumgarten G, Taffet GE, Ballantyne CM, Michael LH, Entman ML (2000) A chronic mouse model of myocardial ischemia-reperfusion: essential in cytokine studies. Am J Physiol Heart Circ Physiol 278:H1049–H1055. CrossRefPubMedGoogle Scholar
  198. 198.
    O’Connell TD, Swigart PM, Rodrigo MC, Ishizaka S, Joho S, Turnbull L, Tecott LH, Baker AJ, Foster E, Grossman W, Simpson PC (2006) Alpha1-adrenergic receptors prevent a maladaptive cardiac response to pressure overload. J Clin Invest 116:1005–1015. CrossRefPubMedPubMedCentralGoogle Scholar
  199. 199.
    Oka T, Maillet M, Watt AJ, Schwartz RJ, Aronow BJ, Duncan SA, Molkentin JD (2006) Cardiac-specific deletion of Gata4 reveals its requirement for hypertrophy, compensation, and myocyte viability. Circ Res 98:837–845. CrossRefPubMedGoogle Scholar
  200. 200.
    Opavsky MA, Penninger J, Aitken K, Wen WH, Dawood F, Mak T, Liu P (1999) Susceptibility to myocarditis is dependent on the response of alphabeta T lymphocytes to coxsackieviral infection. Circ Res 85:551–558. CrossRefPubMedGoogle Scholar
  201. 201.
    Owan TE, Hodge DO, Herges RM, Jacobsen SJ, Roger VL, Redfield MM (2006) Trends in prevalence and outcome of heart failure with preserved ejection fraction. N Engl J Med 355:251–259. CrossRefPubMedPubMedCentralGoogle Scholar
  202. 202.
    Oyama J, Blais C Jr, Liu X, Pu M, Kobzik L, Kelly RA, Bourcier T (2004) Reduced myocardial ischemia-reperfusion injury in toll-like receptor 4-deficient mice. Circulation 109:784–789. CrossRefPubMedGoogle Scholar
  203. 203.
    Papageorgiou AP, Swinnen M, Vanhoutte D, VandenDriessche T, Chuah M, Lindner D, Verhesen W, de Vries B, D’Hooge J, Lutgens E, Westermann D, Carmeliet P, Heymans S (2012) Thrombospondin-2 prevents cardiac injury and dysfunction in viral myocarditis through the activation of regulatory T-cells. Cardiovasc Res 94:115–124. CrossRefPubMedGoogle Scholar
  204. 204.
    Patel B, Bansal SS, Ismahil MA, Hamid T, Rokosh G, Mack M, Prabhu SD (2018) CCR2(+) monocyte-derived infiltrating macrophages are required for adverse cardiac remodeling during pressure overload. JACC Basic Transl Sci 3:230–244. CrossRefPubMedPubMedCentralGoogle Scholar
  205. 205.
    Paul M, Poyan Mehr A, Kreutz R (2006) Physiology of local renin-angiotensin systems. Physiol Rev 86:747–803. CrossRefPubMedGoogle Scholar
  206. 206.
    Peng H, Yang XP, Carretero OA, Nakagawa P, D’Ambrosio M, Leung P, Xu J, Peterson EL, Gonzalez GE, Harding P, Rhaleb NE (2011) Angiotensin II-induced dilated cardiomyopathy in Balb/c but not C57BL/6 J mice. Exp Physiol 96:756–764. CrossRefPubMedPubMedCentralGoogle Scholar
  207. 207.
    Pfeffer MA, Pfeffer JM, Fishbein MC, Fletcher PJ, Spadaro J, Kloner RA, Braunwald E (1979) Myocardial infarct size and ventricular function in rats. Circ Res 44:503–512. CrossRefPubMedGoogle Scholar
  208. 208.
    Pinkert S, Westermann D, Wang X, Klingel K, Dorner A, Savvatis K, Grossl T, Krohn S, Tschope C, Zeichhardt H, Kotsch K, Weitmann K, Hoffmann W, Schultheiss HP, Spiller OB, Poller W, Fechner H (2009) Prevention of cardiac dysfunction in acute coxsackievirus B3 cardiomyopathy by inducible expression of a soluble coxsackievirus-adenovirus receptor. Circulation 120:2358–2366. CrossRefPubMedGoogle Scholar
  209. 209.
    Pinto AR, Ilinykh A, Ivey MJ, Kuwabara JT, D’Antoni ML, Debuque R, Chandran A, Wang L, Arora K, Rosenthal NA, Tallquist MD (2016) Revisiting cardiac cellular composition. Circ Res 118:400–409. CrossRefPubMedGoogle Scholar
  210. 210.
    Ponta H, Sherman L, Herrlich PA (2003) CD44: from adhesion molecules to signalling regulators. Nat Rev Mol Cell Biol 4:33–45. CrossRefPubMedGoogle Scholar
  211. 211.
    Prabhu SD, Frangogiannis NG (2016) The biological basis for cardiac repair after myocardial infarction: from inflammation to fibrosis. Circ Res 119:91–112. CrossRefPubMedPubMedCentralGoogle Scholar
  212. 212.
    Proudfoot AE, Handel TM, Johnson Z, Lau EK, LiWang P, Clark-Lewis I, Borlat F, Wells TN, Kosco-Vilbois MH (2003) Glycosaminoglycan binding and oligomerization are essential for the in vivo activity of certain chemokines. Proc Natl Acad Sci USA 100:1885–1890. CrossRefPubMedGoogle Scholar
  213. 213.
    Rai V, Sharma P, Agrawal S, Agrawal DK (2017) Relevance of mouse models of cardiac fibrosis and hypertrophy in cardiac research. Mol Cell Biochem 424:123–145. CrossRefPubMedGoogle Scholar
  214. 214.
    Regan JA, Mauro AG, Carbone S, Marchetti C, Gill R, Mezzaroma E, Valle Raleigh J, Salloum FN, Van Tassell BW, Abbate A, Toldo S (2015) A mouse model of heart failure with preserved ejection fraction due to chronic infusion of a low subpressor dose of angiotensin II. Am J Physiol Heart Circ Physiol 309:H771–H778. CrossRefPubMedPubMedCentralGoogle Scholar
  215. 215.
    Ren G, Michael LH, Entman ML, Frangogiannis NG (2002) Morphological characteristics of the microvasculature in healing myocardial infarcts. J Histochem Cytochem 50:71–79. CrossRefPubMedGoogle Scholar
  216. 216.
    Richards DA, Bao W, Rambo MV, Burgert M, Jucker BM, Lenhard SC (2013) Examining the relationship between exercise tolerance and isoproterenol-based cardiac reserve in murine models of heart failure. J Appl Physiol (1985) 114:1202–1210. CrossRefGoogle Scholar
  217. 217.
    Rickard AJ, Morgan J, Bienvenu LA, Fletcher EK, Cranston GA, Shen JZ, Reichelt ME, Delbridge LM, Young MJ (2012) Cardiomyocyte mineralocorticoid receptors are essential for deoxycorticosterone/salt-mediated inflammation and cardiac fibrosis. Hypertension 60:1443–1450. CrossRefPubMedGoogle Scholar
  218. 218.
    Rickard AJ, Morgan J, Chrissobolis S, Miller AA, Sobey CG, Young MJ (2014) Endothelial cell mineralocorticoid receptors regulate deoxycorticosterone/salt-mediated cardiac remodeling and vascular reactivity but not blood pressure. Hypertension 63:1033–1040. CrossRefPubMedGoogle Scholar
  219. 219.
    Rickard AJ, Morgan J, Tesch G, Funder JW, Fuller PJ, Young MJ (2009) Deletion of mineralocorticoid receptors from macrophages protects against deoxycorticosterone/salt-induced cardiac fibrosis and increased blood pressure. Hypertension 54:537–543. CrossRefPubMedGoogle Scholar
  220. 220.
    Rienks M, Carai P, Bitsch N, Schellings M, Vanhaverbeke M, Verjans J, Cuijpers I, Heymans S, Papageorgiou A (2017) Sema3A promotes the resolution of cardiac inflammation after myocardial infarction. Basic Res Cardiol 112:42. CrossRefPubMedPubMedCentralGoogle Scholar
  221. 221.
    Rienks M, Papageorgiou AP (2016) Novel regulators of cardiac inflammation: matricellular proteins expand their repertoire. J Mol Cell Cardiol 91:172–178. CrossRefPubMedGoogle Scholar
  222. 222.
    Rifkin DB, Mazzieri R, Munger JS, Noguera I, Sung J (1999) Proteolytic control of growth factor availability. APMIS 107:80–85. CrossRefPubMedGoogle Scholar
  223. 223.
    Roberts BJ, Dragon JA, Moussawi M, Huber SA (2012) Sex-specific signaling through Toll-Like Receptors 2 and 4 contributes to survival outcome of Coxsackievirus B3 infection in C57Bl/6 mice. Biol Sex Differ 3:25. CrossRefPubMedPubMedCentralGoogle Scholar
  224. 224.
    Roberts BJ, Moussawi M, Huber SA (2013) Sex differences in TLR2 and TLR4 expression and their effect on coxsackievirus-induced autoimmune myocarditis. Exp Mol Pathol 94:58–64. CrossRefPubMedGoogle Scholar
  225. 225.
    Rockman HA, Ross RS, Harris AN, Knowlton KU, Steinhelper ME, Field LJ, Ross J Jr, Chien KR (1991) Segregation of atrial-specific and inducible expression of an atrial natriuretic factor transgene in an in vivo murine model of cardiac hypertrophy. Proc Natl Acad Sci USA 88:8277–8281. CrossRefPubMedGoogle Scholar
  226. 226.
    Rose NR (2014) Learning from myocarditis: mimicry, chaos and black holes. F1000Prime Rep 6:25. CrossRefPubMedPubMedCentralGoogle Scholar
  227. 227.
    Rosin NL, Sopel MJ, Falkenham A, Lee TD, Legare JF (2015) Disruption of collagen homeostasis can reverse established age-related myocardial fibrosis. Am J Pathol 185:631–642. CrossRefPubMedGoogle Scholar
  228. 228.
    Salvador AM, Moss ME, Aronovitz M, Mueller KB, Blanton RM, Jaffe IZ, Alcaide P (2017) Endothelial mineralocorticoid receptor contributes to systolic dysfunction induced by pressure overload without modulating cardiac hypertrophy or inflammation. Physiol Rep. CrossRefPubMedPubMedCentralGoogle Scholar
  229. 229.
    Saxena A, Chen W, Su Y, Rai V, Uche OU, Li N, Frangogiannis NG (2013) IL-1 induces proinflammatory leukocyte infiltration and regulates fibroblast phenotype in the infarcted myocardium. J Immunol 191:4838–4848. CrossRefPubMedGoogle Scholar
  230. 230.
    Schellings MW, Vanhoutte D, Swinnen M, Cleutjens JP, Debets J, van Leeuwen RE, d’Hooge J, Van de Werf F, Carmeliet P, Pinto YM, Sage EH, Heymans S (2009) Absence of SPARC results in increased cardiac rupture and dysfunction after acute myocardial infarction. J Exp Med 206:113–123. CrossRefPubMedPubMedCentralGoogle Scholar
  231. 231.
    Schiller M, Javelaud D, Mauviel A (2004) TGF-beta-induced SMAD signaling and gene regulation: consequences for extracellular matrix remodeling and wound healing. J Dermatol Sci 35:83–92. CrossRefPubMedGoogle Scholar
  232. 232.
    Schloss MJ, Horckmans M, Nitz K, Duchene J, Drechsler M, Bidzhekov K, Scheiermann C, Weber C, Soehnlein O, Steffens S (2016) The time-of-day of myocardial infarction onset affects healing through oscillations in cardiac neutrophil recruitment. EMBO Mol Med 8:937–948. CrossRefPubMedPubMedCentralGoogle Scholar
  233. 233.
    Schroder K, Tschopp J (2010) The inflammasomes. Cell 140:821–832. CrossRefPubMedGoogle Scholar
  234. 234.
    Schroen B, Heymans S, Sharma U, Blankesteijn WM, Pokharel S, Cleutjens JP, Porter JG, Evelo CT, Duisters R, van Leeuwen RE, Janssen BJ, Debets JJ, Smits JF, Daemen MJ, Crijns HJ, Bornstein P, Pinto YM (2004) Thrombospondin-2 is essential for myocardial matrix integrity: increased expression identifies failure-prone cardiac hypertrophy. Circ Res 95:515–522. CrossRefPubMedGoogle Scholar
  235. 235.
    Schultheiss HP, Kuhl U, Cooper LT (2011) The management of myocarditis. Eur Heart J 32:2616–2625. CrossRefPubMedGoogle Scholar
  236. 236.
    Schultz JC, Hilliard AA, Cooper LT Jr, Rihal CS (2009) Diagnosis and treatment of viral myocarditis. Mayo Clin Proc 84:1001–1009. CrossRefPubMedPubMedCentralGoogle Scholar
  237. 237.
    Schultz Jel J, Witt SA, Glascock BJ, Nieman ML, Reiser PJ, Nix SL, Kimball TR, Doetschman T (2002) TGF-beta1 mediates the hypertrophic cardiomyocyte growth induced by angiotensin II. J Clin Invest 109:787–796. CrossRefPubMedGoogle Scholar
  238. 238.
    Serini G, Bochaton-Piallat ML, Ropraz P, Geinoz A, Borsi L, Zardi L, Gabbiani G (1998) The fibronectin domain ED-A is crucial for myofibroblastic phenotype induction by transforming growth factor-beta1. J Cell Biol 142:873–881. CrossRefPubMedPubMedCentralGoogle Scholar
  239. 239.
    Shen JZ, Morgan J, Tesch GH, Rickard AJ, Chrissobolis S, Drummond GR, Fuller PJ, Young MJ (2016) Cardiac tissue injury and remodeling is dependent upon MR regulation of activation pathways in cardiac tissue macrophages. Endocrinology 157:3213–3223. CrossRefPubMedGoogle Scholar
  240. 240.
    Shen Y, Cheng F, Sharma M, Merkulova Y, Raithatha SA, Parkinson LG, Zhao H, Westendorf K, Bohunek L, Bozin T, Hsu I, Ang LS, Williams SJ, Bleackley RC, Eriksson JE, Seidman MA, McManus BM, Granville DJ (2016) Granzyme B deficiency protects against angiotensin II-induced cardiac fibrosis. Am J Pathol 186:87–100. CrossRefPubMedGoogle Scholar
  241. 241.
    Shi Y, Chen C, Lisewski U, Wrackmeyer U, Radke M, Westermann D, Sauter M, Tschope C, Poller W, Klingel K, Gotthardt M (2009) Cardiac deletion of the Coxsackievirus-adenovirus receptor abolishes Coxsackievirus B3 infection and prevents myocarditis in vivo. J Am Coll Cardiol 53:1219–1226. CrossRefPubMedGoogle Scholar
  242. 242.
    Shi Y, Massague J (2003) Mechanisms of TGF-beta signaling from cell membrane to the nucleus. Cell 113:685–700. CrossRefPubMedGoogle Scholar
  243. 243.
    Shinde AV, Frangogiannis NG (2014) Fibroblasts in myocardial infarction: a role in inflammation and repair. J Mol Cell Cardiol 70:74–82. CrossRefPubMedGoogle Scholar
  244. 244.
    Silberman GA, Fan TH, Liu H, Jiao Z, Xiao HD, Lovelock JD, Boulden BM, Widder J, Fredd S, Bernstein KE, Wolska BM, Dikalov S, Harrison DG, Dudley SC Jr (2010) Uncoupled cardiac nitric oxide synthase mediates diastolic dysfunction. Circulation 121:519–528. CrossRefPubMedPubMedCentralGoogle Scholar
  245. 245.
    Singer AJ, Clark RA (1999) Cutaneous wound healing. N Engl J Med 341:738–746. CrossRefPubMedGoogle Scholar
  246. 246.
    Soehnlein O, Lindbom L (2010) Phagocyte partnership during the onset and resolution of inflammation. Nat Rev Immunol 10:427–439. CrossRefPubMedGoogle Scholar
  247. 247.
    Sorokin L (2010) The impact of the extracellular matrix on inflammation. Nat Rev Immunol 10:712–723. CrossRefPubMedGoogle Scholar
  248. 248.
    Sriramula S, Francis J (2015) Tumor necrosis factor—alpha is essential for angiotensin II-induced ventricular remodeling: role for oxidative stress. PLoS One 10:e0138372. CrossRefPubMedPubMedCentralGoogle Scholar
  249. 249.
    Suryakumar G, Kasiganesan H, Balasubramanian S, Kuppuswamy D (2010) Lack of beta3 integrin signaling contributes to calpain-mediated myocardial cell loss in pressure-overloaded myocardium. J Cardiovasc Pharmacol 55:567–573. CrossRefPubMedPubMedCentralGoogle Scholar
  250. 250.
    Szabo Z, Magga J, Alakoski T, Ulvila J, Piuhola J, Vainio L, Kivirikko KI, Vuolteenaho O, Ruskoaho H, Lipson KE, Signore P, Kerkela R (2014) Connective tissue growth factor inhibition attenuates left ventricular remodeling and dysfunction in pressure overload-induced heart failure. Hypertension 63:1235–1240. CrossRefPubMedGoogle Scholar
  251. 251.
    Takeda K, Akira S (2005) Toll-like receptors in innate immunity. Int Immunol 17:1–14. CrossRefGoogle Scholar
  252. 252.
    Takimoto E, Champion HC, Li M, Belardi D, Ren S, Rodriguez ER, Bedja D, Gabrielson KL, Wang Y, Kass DA (2005) Chronic inhibition of cyclic GMP phosphodiesterase 5A prevents and reverses cardiac hypertrophy. Nat Med 11:214–222. CrossRefPubMedGoogle Scholar
  253. 253.
    Tang TT, Yuan J, Zhu ZF, Zhang WC, Xiao H, Xia N, Yan XX, Nie SF, Liu J, Zhou SF, Li JJ, Yao R, Liao MY, Tu X, Liao YH, Cheng X (2012) Regulatory T cells ameliorate cardiac remodeling after myocardial infarction. Basic Res Cardiol 107:232. CrossRefPubMedGoogle Scholar
  254. 254.
    Tank J, Lindner D, Wang X, Stroux A, Gilke L, Gast M, Zietsch C, Skurk C, Scheibenbogen C, Klingel K, Lassner D, Kuhl U, Schultheiss HP, Westermann D, Poller W (2014) Single-target RNA interference for the blockade of multiple interacting proinflammatory and profibrotic pathways in cardiac fibroblasts. J Mol Cell Cardiol 66:141–156. CrossRefPubMedGoogle Scholar
  255. 255.
    Tesch GH, Young MJ (2017) Mineralocorticoid receptor signaling as a therapeutic target for renal and cardiac fibrosis. Front Pharmacol 8:313. CrossRefPubMedPubMedCentralGoogle Scholar
  256. 256.
    Thygesen K, Alpert JS, Jaffe AS, Chaitman BR, Bax JJ, Morrow DA, White HD, Executive Group on behalf of the Joint European Society of Cardiology/American College of Cardiology/American Heart Association/World Heart Federation Task Force for the Universal Definition of Myocardial I (2018) Fourth universal definition of myocardial infarction (2018). Circulation 138:e618–e651. CrossRefPubMedGoogle Scholar
  257. 257.
    Tian Z, Zheng H, Li J, Li Y, Su H, Wang X (2012) Genetically induced moderate inhibition of the proteasome in cardiomyocytes exacerbates myocardial ischemia-reperfusion injury in mice. Circ Res 111:532–542. CrossRefPubMedPubMedCentralGoogle Scholar
  258. 258.
    Trueblood NA, Xie Z, Communal C, Sam F, Ngoy S, Liaw L, Jenkins AW, Wang J, Sawyer DB, Bing OH, Apstein CS, Colucci WS, Singh K (2001) Exaggerated left ventricular dilation and reduced collagen deposition after myocardial infarction in mice lacking osteopontin. Circ Res 88:1080–1087. CrossRefPubMedGoogle Scholar
  259. 259.
    Usher MG, Duan SZ, Ivaschenko CY, Frieler RA, Berger S, Schutz G, Lumeng CN, Mortensen RM (2010) Myeloid mineralocorticoid receptor controls macrophage polarization and cardiovascular hypertrophy and remodeling in mice. J Clin Invest 120:3350–3364. CrossRefPubMedPubMedCentralGoogle Scholar
  260. 260.
    Valero-Munoz M, Backman W, Sam F (2017) Murine models of heart failure with preserved ejection fraction: a “fishing expedition”. JACC Basic Transl Sci 2:770–789. CrossRefPubMedPubMedCentralGoogle Scholar
  261. 261.
    Valero-Munoz M, Li S, Wilson RM, Hulsmans M, Aprahamian T, Fuster JJ, Nahrendorf M, Scherer PE, Sam F (2016) Heart failure with preserved ejection fraction induces beiging in adipose tissue. Circ Heart Fail 9:e002724. CrossRefPubMedPubMedCentralGoogle Scholar
  262. 262.
    Virag JI, Murry CE (2003) Myofibroblast and endothelial cell proliferation during murine myocardial infarct repair. Am J Pathol 163:2433–2440. CrossRefPubMedPubMedCentralGoogle Scholar
  263. 263.
    Wang N, Liang H, Zen K (2014) Molecular mechanisms that influence the macrophage m1-m2 polarization balance. Front Immunol 5:614. CrossRefPubMedPubMedCentralGoogle Scholar
  264. 264.
    Weathington NM, van Houwelingen AH, Noerager BD, Jackson PL, Kraneveld AD, Galin FS, Folkerts G, Nijkamp FP, Blalock JE (2006) A novel peptide CXCR ligand derived from extracellular matrix degradation during airway inflammation. Nat Med 12:317–323. CrossRefGoogle Scholar
  265. 265.
    Weber KT (1989) Cardiac interstitium in health and disease: the fibrillar collagen network. J Am Coll Cardiol 13:1637–1652. CrossRefPubMedGoogle Scholar
  266. 266.
    Weinberg SE, Sena LA, Chandel NS (2015) Mitochondria in the regulation of innate and adaptive immunity. Immunity 42:406–417. CrossRefPubMedPubMedCentralGoogle Scholar
  267. 267.
    Weinzierl AO, Szalay G, Wolburg H, Sauter M, Rammensee HG, Kandolf R, Stevanovic S, Klingel K (2008) Effective chemokine secretion by dendritic cells and expansion of cross-presenting CD4-/CD8 + dendritic cells define a protective phenotype in the mouse model of coxsackievirus myocarditis. J Virol 82:8149–8160. CrossRefPubMedPubMedCentralGoogle Scholar
  268. 268.
    Weithauser A, Rauch U (2014) Role of protease-activated receptors for the innate immune response of the heart. Trends Cardiovasc Med 24:249–255. CrossRefPubMedGoogle Scholar
  269. 269.
    Wessely R, Klingel K, Knowlton KU, Kandolf R (2001) Cardioselective infection with coxsackievirus B3 requires intact type I interferon signaling: implications for mortality and early viral replication. Circulation 103:756–761. CrossRefPubMedGoogle Scholar
  270. 270.
    Wessely R, Klingel K, Santana LF, Dalton N, Hongo M, Jonathan Lederer W, Kandolf R, Knowlton KU (1998) Transgenic expression of replication-restricted enteroviral genomes in heart muscle induces defective excitation-contraction coupling and dilated cardiomyopathy. J Clin Invest 102:1444–1453. CrossRefPubMedPubMedCentralGoogle Scholar
  271. 271.
    Westermann D, Becher PM, Lindner D, Savvatis K, Xia Y, Frohlich M, Hoffmann S, Schultheiss HP, Tschope C (2012) Selective PDE5A inhibition with sildenafil rescues left ventricular dysfunction, inflammatory immune response and cardiac remodeling in angiotensin II-induced heart failure in vivo. Basic Res Cardiol 107:308. CrossRefPubMedGoogle Scholar
  272. 272.
    Westermann D, Heymans S (2014) Fibrosis or hypertrophy: let TIMPs decide. Cardiovasc Res 103:196–197. CrossRefPubMedGoogle Scholar
  273. 273.
    Westermann D, Mersmann J, Melchior A, Freudenberger T, Petrik C, Schaefer L, Lullmann-Rauch R, Lettau O, Jacoby C, Schrader J, Brand-Herrmann SM, Young MF, Schultheiss HP, Levkau B, Baba HA, Unger T, Zacharowski K, Tschope C, Fischer JW (2008) Biglycan is required for adaptive remodeling after myocardial infarction. Circulation 117:1269–1276. CrossRefPubMedGoogle Scholar
  274. 274.
    Westermann D, Savvatis K, Lindner D, Zietsch C, Becher PM, Hammer E, Heimesaat MM, Bereswill S, Volker U, Escher F, Riad A, Plendl J, Klingel K, Poller W, Schultheiss HP, Tschope C (2011) Reduced degradation of the chemokine MCP-3 by matrix metalloproteinase-2 exacerbates myocardial inflammation in experimental viral cardiomyopathy. Circulation 124:2082–2093. CrossRefPubMedGoogle Scholar
  275. 275.
    Westermann D, Savvatis K, Schultheiss HP, Tschope C (2010) Immunomodulation and matrix metalloproteinases in viral myocarditis. J Mol Cell Cardiol 48:468–473. CrossRefPubMedGoogle Scholar
  276. 276.
    Willems IE, Havenith MG, De Mey JG, Daemen MJ (1994) The alpha-smooth muscle actin-positive cells in healing human myocardial scars. Am J Pathol 145:868–875PubMedPubMedCentralGoogle Scholar
  277. 277.
    Witt H, Schubert C, Jaekel J, Fliegner D, Penkalla A, Tiemann K, Stypmann J, Roepcke S, Brokat S, Mahmoodzadeh S, Brozova E, Davidson MM, Ruiz Noppinger P, Grohe C, Regitz-Zagrosek V (2008) Sex-specific pathways in early cardiac response to pressure overload in mice. J Mol Med (Berl) 86:1013–1024. CrossRefGoogle Scholar
  278. 278.
    Woodall MC, Woodall BP, Gao E, Yuan A, Koch WJ (2016) Cardiac fibroblast GRK2 deletion enhances contractility and remodeling following ischemia/reperfusion injury. Circ Res 119:1116–1127. CrossRefPubMedPubMedCentralGoogle Scholar
  279. 279.
    Woodiwiss AJ, Tsotetsi OJ, Sprott S, Lancaster EJ, Mela T, Chung ES, Meyer TE, Norton GR (2001) Reduction in myocardial collagen cross-linking parallels left ventricular dilatation in rat models of systolic chamber dysfunction. Circulation 103:155–160. CrossRefPubMedGoogle Scholar
  280. 280.
    Xia Y, Lee K, Li N, Corbett D, Mendoza L, Frangogiannis NG (2009) Characterization of the inflammatory and fibrotic response in a mouse model of cardiac pressure overload. Histochem Cell Biol 131:471–481. CrossRefPubMedGoogle Scholar
  281. 281.
    Xiao H, Li H, Wang JJ, Zhang JS, Shen J, An XB, Zhang CC, Wu JM, Song Y, Wang XY, Yu HY, Deng XN, Li ZJ, Xu M, Lu ZZ, Du J, Gao W, Zhang AH, Feng Y, Zhang YY (2018) IL-18 cleavage triggers cardiac inflammation and fibrosis upon beta-adrenergic insult. Eur Heart J 39:60–69. CrossRefPubMedGoogle Scholar
  282. 282.
    Xiong D, Yajima T, Lim BK, Stenbit A, Dublin A, Dalton ND, Summers-Torres D, Molkentin JD, Duplain H, Wessely R, Chen J, Knowlton KU (2007) Inducible cardiac-restricted expression of enteroviral protease 2A is sufficient to induce dilated cardiomyopathy. Circulation 115:94–102. CrossRefPubMedGoogle Scholar
  283. 283.
    Xu S, Zhi H, Hou X, Cohen RA, Jiang B (2011) IkappaBbeta attenuates angiotensin II-induced cardiovascular inflammation and fibrosis in mice. Hypertension 58:310–316. CrossRefPubMedPubMedCentralGoogle Scholar
  284. 284.
    Yajima T, Knowlton KU (2009) Viral myocarditis: from the perspective of the virus. Circulation 119:2615–2624. CrossRefPubMedGoogle Scholar
  285. 285.
    Yan X, Anzai A, Katsumata Y, Matsuhashi T, Ito K, Endo J, Yamamoto T, Takeshima A, Shinmura K, Shen W, Fukuda K, Sano M (2013) Temporal dynamics of cardiac immune cell accumulation following acute myocardial infarction. J Mol Cell Cardiol 62:24–35. CrossRefPubMedGoogle Scholar
  286. 286.
    Yang F, Liu YH, Yang XP, Xu J, Kapke A, Carretero OA (2002) Myocardial infarction and cardiac remodelling in mice. Exp Physiol 87:547–555. CrossRefPubMedGoogle Scholar
  287. 287.
    Yang XP, Liu YH, Scicli GM, Webb CR, Carretero OA (1997) Role of kinins in the cardioprotective effect of preconditioning: study of myocardial ischemia/reperfusion injury in B2 kinin receptor knockout mice and kininogen-deficient rats. Hypertension 30:735–740. CrossRefPubMedGoogle Scholar
  288. 288.
    Yu Q, Stamenkovic I (2000) Cell surface-localized matrix metalloproteinase-9 proteolytically activates TGF-beta and promotes tumor invasion and angiogenesis. Genes Dev 14:163–176. CrossRefPubMedPubMedCentralGoogle Scholar
  289. 289.
    Zamilpa R, Zhang J, Chiao YA, de Castro Bras LE, Halade GV, Ma Y, Hacker SO, Lindsey ML (2013) Cardiac wound healing post-myocardial infarction: a novel method to target extracellular matrix remodeling in the left ventricle. Methods Mol Biol 1037:313–324. CrossRefPubMedPubMedCentralGoogle Scholar
  290. 290.
    Zaprutko J, Michalak M, Nowicka A, Dankowski R, Drozdz J, Ponikowski P, Opolski G, Nessler J, Nowalany-Kozielska E, Szyszka A (2017) Hospitalisation length and prognosis in heart failure patients. Kardiol Pol 75:323–331. CrossRefPubMedGoogle Scholar
  291. 291.
    Zhou P, Pu WT (2016) Recounting cardiac cellular composition. Circ Res 118:368–370. CrossRefPubMedPubMedCentralGoogle Scholar
  292. 292.
    Zhu M, Goetsch SC, Wang Z, Luo R, Hill JA, Schneider J, Morris SM Jr, Liu ZP (2015) FoxO4 promotes early inflammatory response upon myocardial infarction via endothelial Arg1. Circ Res 117:967–977. CrossRefPubMedPubMedCentralGoogle Scholar
  293. 293.
    Zou Y, Akazawa H, Qin Y, Sano M, Takano H, Minamino T, Makita N, Iwanaga K, Zhu W, Kudoh S, Toko H, Tamura K, Kihara M, Nagai T, Fukamizu A, Umemura S, Iiri T, Fujita T, Komuro I (2004) Mechanical stress activates angiotensin II type 1 receptor without the involvement of angiotensin II. Nat Cell Biol 6:499–506. CrossRefPubMedGoogle Scholar
  294. 294.
    Zymek P, Bujak M, Chatila K, Cieslak A, Thakker G, Entman ML, Frangogiannis NG (2006) The role of platelet-derived growth factor signaling in healing myocardial infarcts. J Am Coll Cardiol 48:2315–2323. CrossRefPubMedGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2019

Authors and Affiliations

  • Lucas Bacmeister
    • 1
    • 2
    Email author
  • Michael Schwarzl
    • 1
    • 2
  • Svenja Warnke
    • 1
    • 2
  • Bastian Stoffers
    • 1
    • 2
  • Stefan Blankenberg
    • 1
    • 2
  • Dirk Westermann
    • 1
    • 2
  • Diana Lindner
    • 1
    • 2
    Email author
  1. 1.Clinic for General and Interventional Cardiology, University Heart Center HamburgUniversity Hospital Hamburg-EppendorfHamburgGermany
  2. 2.DZHK (German Center for Cardiovascular Research), Partner site Hamburg/Kiel/LübeckHamburgGermany

Personalised recommendations