Advertisement

Basic Research in Cardiology

, 113:44 | Cite as

The role of Wnt signaling in the healing myocardium: a focus on cell specificity

  • Ingmar Sören Meyer
  • Florian Leuschner
Review

Abstract

Various cell types are involved in the healing process after myocardial infarction (MI). Besides cardiac resident cells (such as cardiomyocytes, fibroblasts and endothelial cells) already present at the lesion site, a massive influx of leukocytes (mainly monocytes and neutrophils) is observed within hours after the ischemic event. So far, little is known about modes of interaction of these cells. Wnt signaling is an evolutionary conserved signaling cassette known to play an important role in cell–cell communication. While the overall reactivation of Wnt signaling upon ischemic injury is well described, the precise expression pattern of Wnt proteins, however, is far from understood. We here describe known Wnt components that partake in MI healing and differentiate cell-specific aspects. The secretion of Wnt proteins and their antagonists in the context of cardiac inflammation after MI appear to be tightly regulated in a spatial–temporal manner. Overall, we aim to stress the importance of elucidating not only Wnt component-specific aspects, but also their sometimes contradicting effects in different target cells. A better understanding of Wnt signaling in MI healing may eventually lead to the development of successful therapeutic approaches in an often considered “un-druggable” pathway.

Keywords

Myocardial infarction Wnt signaling Inflammation 

Notes

Acknowledgements

FL is supported by the German Research Foundation (DFG, Heisenberg Programm), the German Heart Research Foundation, and the BMBF (German Ministry of Education and Research; Project DeCaRe and Confirm).

Compliance with ethical standards

Conflict of interest

The authors declare that they have no conflict of interest.

References

  1. 1.
    Abraityte A, Vinge LE, Askevold ET, Lekva T, Michelsen AE, Ranheim T, Alfsnes K, Fiane A, Aakhus S, Lunde IG, Dahl CP, Aukrust P, Christensen G, Gullestad L, Yndestad A, Ueland T (2017) Wnt5a is elevated in heart failure and affects cardiac fibroblast function. J Mol Med (Berl) 95:767–777.  https://doi.org/10.1007/s00109-017-1529-1 CrossRefGoogle Scholar
  2. 2.
    Aisagbonhi O, Rai M, Ryzhov S, Atria N, Feoktistov I, Hatzopoulos AK (2011) Experimental myocardial infarction triggers canonical Wnt signaling and endothelial-to-mesenchymal transition. Dis Model Mech 4:469–483.  https://doi.org/10.1242/dmm.006510 CrossRefPubMedPubMedCentralGoogle Scholar
  3. 3.
    Ajima R, Bisson JA, Helt JC, Nakaya MA, Habas R, Tessarollo L, He X, Morrisey EE, Yamaguchi TP, Cohen ED (2015) DAAM1 and DAAM2 are co-required for myocardial maturation and sarcomere assembly. Dev Biol 408:126–139.  https://doi.org/10.1016/j.ydbio.2015.10.003 CrossRefPubMedPubMedCentralGoogle Scholar
  4. 4.
    Assmus B, Iwasaki M, Schachinger V, Roexe T, Koyanagi M, Iekushi K, Xu Q, Tonn T, Seifried E, Liebner S, Kranert WT, Grunwald F, Dimmeler S, Zeiher AM (2012) Acute myocardial infarction activates progenitor cells and increases Wnt signalling in the bone marrow. Eur Heart J 33:1911–1919.  https://doi.org/10.1093/eurheartj/ehr388 CrossRefPubMedPubMedCentralGoogle Scholar
  5. 5.
    Ault KT, Durmowicz G, Galione A, Harger PL, Busa WB (1996) Modulation of Xenopus embryo mesoderm-specific gene expression and dorsoanterior patterning by receptors that activate the phosphatidylinositol cycle signal transduction pathway. Development 122:2033–2041PubMedPubMedCentralGoogle Scholar
  6. 6.
    Barandon L, Casassus F, Leroux L, Moreau C, Allieres C, Lamaziere JM, Dufourcq P, Couffinhal T, Duplaa C (2011) Secreted frizzled-related protein-1 improves postinfarction scar formation through a modulation of inflammatory response. Arterioscler Thromb Vasc Biol 31:e80–e87.  https://doi.org/10.1161/atvbaha.111.232280 CrossRefPubMedPubMedCentralGoogle Scholar
  7. 7.
    Bastakoty D, Young PP (2016) Wnt/β-catenin pathway in tissue injury: roles in pathology and therapeutic opportunities for regeneration. FASEB J 30:3271–3284.  https://doi.org/10.1096/fj.201600502R CrossRefPubMedPubMedCentralGoogle Scholar
  8. 8.
    Bisson JA, Mills B, Paul Helt JC, Zwaka TP, Cohen ED (2015) Wnt5a and Wnt11 inhibit the canonical Wnt pathway and promote cardiac progenitor development via the Caspase-dependent degradation of AKT. Dev Biol 398:80–96.  https://doi.org/10.1016/j.ydbio.2014.11.015 CrossRefPubMedPubMedCentralGoogle Scholar
  9. 9.
    Borrell-Pages M, Vilahur G, Romero JC, Casaní L, Bejar MT, Badimon L (2016) LRP5/canonical Wnt signalling and healing of ischemic myocardium. Basic Res Cardiol 111:67.  https://doi.org/10.1007/s00395-016-0585-y CrossRefPubMedPubMedCentralGoogle Scholar
  10. 10.
    Brade T, Manner J, Kuhl M (2006) The role of Wnt signalling in cardiac development and tissue remodelling in the mature heart. Cardiovasc Res 72:198–209.  https://doi.org/10.1016/j.cardiores.2006.06.025 CrossRefPubMedGoogle Scholar
  11. 11.
    Bradley RS, Brown AM (1990) The proto-oncogene int-1 encodes a secreted protein associated with the extracellular matrix. EMBO J 9:1569–1575CrossRefPubMedCentralGoogle Scholar
  12. 12.
    Braunwald E (2013) Coronary plaque erosion: recognition and management. JACC Cardiovasc Imaging 6:288–289.  https://doi.org/10.1016/j.jcmg.2013.01.003 CrossRefPubMedGoogle Scholar
  13. 13.
    Burgy O, Königshoff M (2018) The WNT signaling pathways in wound healing and fibrosis. Matrix Biol.  https://doi.org/10.1016/j.matbio.2018.03.017 CrossRefPubMedGoogle Scholar
  14. 14.
    Cadigan KM, Waterman ML (2012) TCF/LEFs and Wnt signaling in the nucleus. Cold Spring Harb Perspect Biol.  https://doi.org/10.1101/cshperspect.a007906 CrossRefPubMedPubMedCentralGoogle Scholar
  15. 15.
    Cahill TJ, Kharbanda RK (2017) Heart failure after myocardial infarction in the era of primary percutaneous coronary intervention: mechanisms, incidence and identification of patients at risk. World J Cardiol 9:407–415.  https://doi.org/10.4330/wjc.v9.i5.407 CrossRefPubMedPubMedCentralGoogle Scholar
  16. 16.
    Chen Y, Zhang Y, Deng Q, Shan N, Peng W, Luo X, Zhang H, Baker PN, Tong C, Qi H (2016) Inhibition of Wnt inhibitory factor 1 under hypoxic condition in human umbilical vein endothelial cells promoted angiogenesis in vitro. Reprod Sci 23:1348–1358.  https://doi.org/10.1177/1933719116638174 CrossRefPubMedPubMedCentralGoogle Scholar
  17. 17.
    Christia P, Frangogiannis NG (2013) Targeting inflammatory pathways in myocardial infarction. Eur J Clin Invest 43:986–995.  https://doi.org/10.1111/eci.12118 CrossRefPubMedPubMedCentralGoogle Scholar
  18. 18.
    Cruciat CM, Niehrs C (2013) Secreted and transmembrane wnt inhibitors and activators. Cold Spring Harb Perspect Biol 5:a015081.  https://doi.org/10.1101/cshperspect.a015081 CrossRefPubMedPubMedCentralGoogle Scholar
  19. 19.
    Dawson K, Aflaki M, Nattel S (2013) Role of the Wnt-Frizzled system in cardiac pathophysiology: a rapidly developing, poorly understood area with enormous potential. J Physiol 591:1409–1432.  https://doi.org/10.1113/jphysiol.2012.235382 CrossRefPubMedPubMedCentralGoogle Scholar
  20. 20.
    De A (2011) Wnt/Ca2+ signaling pathway: a brief overview. Acta Biochim Biophys Sin (Shanghai) 43:745–756.  https://doi.org/10.1093/abbs/gmr079 CrossRefGoogle Scholar
  21. 21.
    Deb A (2014) Cell-cell interaction in the heart via Wnt/beta-catenin pathway after cardiac injury. Cardiovasc Res 102:214–223.  https://doi.org/10.1093/cvr/cvu054 CrossRefPubMedPubMedCentralGoogle Scholar
  22. 22.
    DeLeon-Pennell KY, Mouton AJ, Ero OK, Ma Y, Padmanabhan Iyer R, Flynn ER, Espinoza I, Musani SK, Vasan RS, Hall ME, Fox ER, Lindsey ML (2018) LXR/RXR signaling and neutrophil phenotype following myocardial infarction classify sex differences in remodeling. Basic Res Cardiol 113:40.  https://doi.org/10.1007/s00395-018-0699-5 CrossRefPubMedPubMedCentralGoogle Scholar
  23. 23.
    Dewald O, Zymek P, Winkelmann K, Koerting A, Ren G, Abou-Khamis T, Michael LH, Rollins BJ, Entman ML, Frangogiannis NG (2005) CCL2/Monocyte chemoattractant protein-1 regulates inflammatory responses critical to healing myocardial infarcts. Circ Res 96:881–889.  https://doi.org/10.1161/01.RES.0000163017.13772.3a CrossRefPubMedGoogle Scholar
  24. 24.
    Duan J, Gherghe C, Liu D, Hamlett E, Srikantha L, Rodgers L, Regan JN, Rojas M, Willis M, Leask A, Majesky M, Deb A (2012) Wnt1/betacatenin injury response activates the epicardium and cardiac fibroblasts to promote cardiac repair. EMBO J 31:429–442.  https://doi.org/10.1038/emboj.2011.418 CrossRefPubMedGoogle Scholar
  25. 25.
    Dutta P, Nahrendorf M (2015) Monocytes in myocardial infarction. Arterioscler Thromb Vasc Biol 35:1066–1070.  https://doi.org/10.1161/ATVBAHA.114.304652 CrossRefPubMedPubMedCentralGoogle Scholar
  26. 26.
    Dutta P, Nahrendorf M (2015) Monocytes in myocardial infarction. Arterioscler Thromb Vasc Biol 35:1066–1070.  https://doi.org/10.1161/atvbaha.114.304652 CrossRefPubMedPubMedCentralGoogle Scholar
  27. 27.
    Famili F, Naber BAE, Vloemans S, de Haas EFE, Tiemessen MM, Staal FJT (2015) Discrete roles of canonical and non-canonical Wnt signaling in hematopoiesis and lymphopoiesis. Cell Death Dis 6:e1981.  https://doi.org/10.1038/cddis.2015.326 CrossRefPubMedPubMedCentralGoogle Scholar
  28. 28.
    Fan J, Qiu L, Shu H, Ma B, Hagenmueller M, Riffel JH, Meryer S, Zhang M, Hardt SE, Wang L, Wang DW, Qiu H, Zhou N (2018) Recombinant frizzled1 protein attenuated cardiac hypertrophy after myocardial infarction via the canonical Wnt signaling pathway. Oncotarget 9:3069–3080.  https://doi.org/10.18632/oncotarget.23149 CrossRefPubMedGoogle Scholar
  29. 29.
    Ferreira Tojais N, Peghaire C, Franzl N, Larrieu-Lahargue F, Jaspard B, Reynaud A, Moreau C, Couffinhal T, Duplaa C, Dufourcq P (2014) Frizzled7 controls vascular permeability through the Wnt-canonical pathway and cross-talk with endothelial cell junction complexes. Cardiovasc Res 103:291–303.  https://doi.org/10.1093/cvr/cvu133 CrossRefPubMedGoogle Scholar
  30. 30.
    Frangogiannis NG (2015) Pathophysiology of myocardial infarction. Compr Physiol 5:1841–1875.  https://doi.org/10.1002/cphy.c150006 CrossRefPubMedPubMedCentralGoogle Scholar
  31. 31.
    Frangogiannis NG (2017) The role of transforming growth factor (TGF)-beta in the infarcted myocardium. J Thorac Dis 9:S52–S63.  https://doi.org/10.21037/jtd.2016.11.19 CrossRefPubMedPubMedCentralGoogle Scholar
  32. 32.
    Gomez-Orte E, Saenz-Narciso B, Moreno S, Cabello J (2013) Multiple functions of the noncanonical Wnt pathway. Trends Genet 29:545–553.  https://doi.org/10.1016/j.tig.2013.06.003 CrossRefPubMedPubMedCentralGoogle Scholar
  33. 33.
    Grainger S, Willert K (2018) Mechanisms of Wnt signaling and control. Wiley Interdiscip Rev Syst Biol Med.  https://doi.org/10.1002/wsbm.1422 CrossRefPubMedPubMedCentralGoogle Scholar
  34. 34.
    Gross JC, Chaudhary V, Bartscherer K, Boutros M (2012) Active Wnt proteins are secreted on exosomes. Nat Cell Biol 14:1036–1045.  https://doi.org/10.1038/ncb2574 CrossRefPubMedPubMedCentralGoogle Scholar
  35. 35.
    Gross JC, Zelarayan LC (2018) The mingle-mangle of Wnt signaling and extracellular vesicles: functional Implications for heart research. Front Cardiovasc Med 5:10.  https://doi.org/10.3389/fcvm.2018.00010 CrossRefPubMedPubMedCentralGoogle Scholar
  36. 36.
    Hagenmueller M, Riffel JH, Bernhold E, Fan J, Katus HA, Hardt SE (2014) Dapper-1 is essential for Wnt5a induced cardiomyocyte hypertrophy by regulating the Wnt/PCP pathway. FEBS Lett 588:2230–2237.  https://doi.org/10.1016/j.febslet.2014.05.039 CrossRefPubMedPubMedCentralGoogle Scholar
  37. 37.
    Hagenmueller M, Riffel JH, Bernhold E, Fan J, Zhang M, Ochs M, Steinbeisser H, Katus HA, Hardt SE (2013) Dapper-1 induces myocardial remodeling through activation of canonical Wnt signaling in cardiomyocytes. Hypertension 61:1177–1183.  https://doi.org/10.1161/hypertensionaha.111.00391 CrossRefPubMedPubMedCentralGoogle Scholar
  38. 38.
    He TC, Sparks AB, Rago C, Hermeking H, Zawel L, da Costa LT, Morin PJ, Vogelstein B, Kinzler KW (1998) Identification of c-MYC as a target of the APC pathway. Science 281:1509–1512CrossRefPubMedCentralGoogle Scholar
  39. 39.
    He W, Zhang L, Ni A, Zhang Z, Mirotsou M, Mao L, Pratt RE, Dzau VJ (2010) Exogenously administered secreted frizzled related protein 2 (Sfrp2) reduces fibrosis and improves cardiac function in a rat model of myocardial infarction. Proc Natl Acad Sci U S A 107:21110–21115.  https://doi.org/10.1073/pnas.1004708107 CrossRefPubMedPubMedCentralGoogle Scholar
  40. 40.
    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.  https://doi.org/10.1093/eurheartj/ehw224 CrossRefPubMedPubMedCentralGoogle Scholar
  41. 41.
    Heusch G, Libby P, Gersh B, Yellon D, Böhm M, Lopaschuk G, Opie L (2014) Lancet seminar: cardiovascular remodelling in coronary artery disease and heart failure. Lancet 383:1933–1943.  https://doi.org/10.1016/S0140-6736(14)60107-0 CrossRefPubMedPubMedCentralGoogle Scholar
  42. 42.
    Hilgendorf I, Gerhardt LM, Tan TC, Winter C, Holderried TA, Chousterman BG, Iwamoto Y, Liao R, Zirlik A, Scherer-Crosbie M, Hedrick CC, Libby P, Nahrendorf M, Weissleder R, Swirski FK (2014) Ly-6Chigh monocytes depend on Nr4a1 to balance both inflammatory and reparative phases in the infarcted myocardium. Circ Res 114:1611–1622.  https://doi.org/10.1161/circresaha.114.303204 CrossRefPubMedPubMedCentralGoogle Scholar
  43. 43.
    Ho HY, Susman MW, Bikoff JB, Ryu YK, Jonas AM, Hu L, Kuruvilla R, Greenberg ME (2012) Wnt5a-Ror-dishevelled signaling constitutes a core developmental pathway that controls tissue morphogenesis. Proc Natl Acad Sci USA 109:4044–4051.  https://doi.org/10.1073/pnas.1200421109 CrossRefPubMedPubMedCentralGoogle Scholar
  44. 44.
    Hofmann U, Beyersdorf N, Weirather J, Podolskaya A, Bauersachs J, Ertl G, Kerkau T, Frantz S (2012) Activation of CD4+ T lymphocytes improves wound healing and survival after experimental myocardial infarction in mice. Circulation 125:1652–1663.  https://doi.org/10.1161/circulationaha.111.044164 CrossRefPubMedPubMedCentralGoogle Scholar
  45. 45.
    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.  https://doi.org/10.1093/eurheartj/ehw002 CrossRefPubMedPubMedCentralGoogle Scholar
  46. 46.
    Houschyar KS, Chelliah MP, Rein S, Maan ZN, Weissenberg K, Duscher D, Branski LK, Siemers F (2018) Role of Wnt signaling during inflammation and sepsis: a review of the literature. Int J Artif Organs.  https://doi.org/10.1177/0391398818762357 CrossRefPubMedPubMedCentralGoogle Scholar
  47. 47.
    Hulin A, Moore V, James JM, Yutzey KE (2017) Loss of Axin2 results in impaired heart valve maturation and subsequent myxomatous valve disease. Cardiovasc Res 113:40–51.  https://doi.org/10.1093/cvr/cvw229 CrossRefPubMedPubMedCentralGoogle Scholar
  48. 48.
    Jiang Y, He X, Howe PH (2012) Disabled-2 (Dab2) inhibits Wnt/beta-catenin signalling by binding LRP6 and promoting its internalization through clathrin. EMBO J 31:2336–2349.  https://doi.org/10.1038/emboj.2012.83 CrossRefPubMedPubMedCentralGoogle Scholar
  49. 49.
    Jung K, Kim P, Leuschner F, Gorbatov R, Kim JK, Ueno T, Nahrendorf M, Yun SH (2013) Endoscopic time-lapse imaging of immune cells in infarcted mouse hearts. Circ Res 112:891–899.  https://doi.org/10.1161/circresaha.111.300484 CrossRefPubMedPubMedCentralGoogle Scholar
  50. 50.
    Jung M, Ma Y, Iyer RP, DeLeon-Pennell KY, Yabluchanskiy A, Garrett MR, Lindsey ML (2017) IL-10 improves cardiac remodeling after myocardial infarction by stimulating M2 macrophage polarization and fibroblast activation. Basic Res Cardiol 112:33.  https://doi.org/10.1007/s00395-017-0622-5 CrossRefPubMedPubMedCentralGoogle Scholar
  51. 51.
    Jung YS, Lee HY, Kim SD, Park JS, Kim JK, Suh PG, Bae YS (2013) Wnt5a stimulates chemotactic migration and chemokine production in human neutrophils. Exp Mol Med 45:e27.  https://doi.org/10.1038/emm.2013.48 CrossRefPubMedGoogle Scholar
  52. 52.
    Kong Q, Dai L, Wang Y, Zhang X, Li C, Jiang S, Li Y, Ding Z, Liu L (2016) HSPA12B attenuated acute myocardial ischemia/reperfusion injury via maintaining endothelial integrity in a PI3K/Akt/mTOR-dependent mechanism. Sci Rep 6:33636.  https://doi.org/10.1038/srep33636 CrossRefPubMedPubMedCentralGoogle Scholar
  53. 53.
    Korn C, Scholz B, Hu J, Srivastava K, Wojtarowicz J, Arnsperger T, Adams RH, Boutros M, Augustin HG, Augustin I (2014) Endothelial cell-derived non-canonical Wnt ligands control vascular pruning in angiogenesis. Development 141:1757–1766.  https://doi.org/10.1242/dev.104422 CrossRefPubMedGoogle Scholar
  54. 54.
    Kuhl M, Sheldahl LC, Park M, Miller JR, Moon RT (2000) The Wnt/Ca2+ pathway: a new vertebrate Wnt signaling pathway takes shape. Trends Genet 16:279–283CrossRefGoogle Scholar
  55. 55.
    Laeremans H, Rensen SS, Ottenheijm HC, Smits JF, Blankesteijn WM (2010) Wnt/frizzled signalling modulates the migration and differentiation of immortalized cardiac fibroblasts. Cardiovasc Res 87:514–523.  https://doi.org/10.1093/cvr/cvq067 CrossRefPubMedGoogle Scholar
  56. 56.
    Lengfeld JE, Lutz SE, Smith JR, Diaconu C, Scott C, Kofman SB, Choi C, Walsh CM, Raine CS, Agalliu I, Agalliu D (2017) Endothelial Wnt/beta-catenin signaling reduces immune cell infiltration in multiple sclerosis. Proc Natl Acad Sci USA 114:E1168–E1177.  https://doi.org/10.1073/pnas.1609905114 CrossRefPubMedGoogle Scholar
  57. 57.
    Leuschner F, Rauch PJ, Ueno T, Gorbatov R, Marinelli B, Lee WW, Dutta P, Wei Y, Robbins C, Iwamoto Y, Sena B, Chudnovskiy A, Panizzi P, Keliher E, Higgins JM, Libby P, Moskowitz MA, Pittet MJ, Swirski FK, Weissleder R, Nahrendorf M (2012) Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis. J Exp Med 209:123–137.  https://doi.org/10.1084/jem.20111009 CrossRefPubMedPubMedCentralGoogle Scholar
  58. 58.
    Lewis EF, Moye LA, Rouleau JL, Sacks FM, Arnold JM, Warnica JW, Flaker GC, Braunwald E, Pfeffer MA (2003) Predictors of late development of heart failure in stable survivors of myocardial infarction: the CARE study. J Am Coll Cardiol 42:1446–1453CrossRefGoogle Scholar
  59. 59.
    Lin H, Angeli M, Chung KJ, Ejimadu C, Rosa AR, Lee T (2016) sFRP2 activates Wnt/beta-catenin signaling in cardiac fibroblasts: differential roles in cell growth, energy metabolism, and extracellular matrix remodeling. Am J Physiol Cell Physiol 311:C710–C719.  https://doi.org/10.1152/ajpcell.00137.2016 CrossRefPubMedPubMedCentralGoogle Scholar
  60. 60.
    Lin JC, Chang RL, Chen YF, Yang JJ, Baskaran R, Chung LC, Chen RJ, Day CH, Vijaya Padma V, Huang CY (2016) beta-Catenin overexpression causes an increase in inflammatory cytokines and NF-kappaB activation in cardiomyocytes. Cell Mol Biol (Noisy-le-grand) 63:17–22.  https://doi.org/10.14715/cmb/2017.63.1.4 CrossRefGoogle Scholar
  61. 61.
    Lin JC, Kuo WW, Baskaran R, Chen MC, Ho TJ, Chen RJ, Chen YF, Vijaya Padma V, Lay IS, Huang CY (2017) Enhancement of beta-catenin in cardiomyocytes suppresses survival protein expression but promotes apoptosis and fibrosis. Cardiol J 24:195–205.  https://doi.org/10.5603/CJ.a2016.0087 CrossRefPubMedGoogle Scholar
  62. 62.
    Lother A, Bergemann S, Deng L, Moser M, Bode C, Hein L (2018) Cardiac endothelial cell transcriptome. Arterioscler Thromb Vasc Biol 38:566–574.  https://doi.org/10.1161/atvbaha.117.310549 CrossRefPubMedGoogle Scholar
  63. 63.
    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.  https://doi.org/10.1093/cvr/cvw024 CrossRefPubMedPubMedCentralGoogle Scholar
  64. 64.
    Ma Y, Yabluchanskiy A, Lindsey ML (2013) Neutrophil roles in left ventricular remodeling following myocardial infarction. Fibrogenesis Tissue Repair 6:11.  https://doi.org/10.1186/1755-1536-6-11 CrossRefPubMedPubMedCentralGoogle Scholar
  65. 65.
    MacDonald BT, Tamai K, He X (2009) Wnt/beta-catenin signaling: components, mechanisms, and diseases. Dev Cell 17:9–26.  https://doi.org/10.1016/j.devcel.2009.06.016 CrossRefPubMedPubMedCentralGoogle Scholar
  66. 66.
    Masckauchan TN, Shawber CJ, Funahashi Y, Li CM, Kitajewski J (2005) Wnt/beta-catenin signaling induces proliferation, survival and interleukin-8 in human endothelial cells. Angiogenesis 8:43–51.  https://doi.org/10.1007/s10456-005-5612-9 CrossRefPubMedGoogle Scholar
  67. 67.
    Mazzotta S, Neves C, Bonner RJ, Bernardo AS, Docherty K, Hoppler S (2016) Distinctive roles of canonical and noncanonical Wnt signaling in human embryonic cardiomyocyte development. Stem Cell Reports 7:764–776.  https://doi.org/10.1016/j.stemcr.2016.08.008 CrossRefPubMedPubMedCentralGoogle Scholar
  68. 68.
    McBride JD, Liu X, Berry WL, Janknecht R, Cheng R, Zhou K, Badiavas EV, J-x Ma (2017) Transgenic expression of a canonical Wnt inhibitor, kallistatin, is associated with decreased circulating CD19+ B lymphocytes in the peripheral blood. Int J Hematol 105:748–757.  https://doi.org/10.1007/s12185-017-2205-5 CrossRefPubMedGoogle Scholar
  69. 69.
    Mewhort HE, Lipon BD, Svystonyuk DA, Teng G, Guzzardi DG, Silva C, Yong VW, Fedak PW (2016) Monocytes increase human cardiac myofibroblast-mediated extracellular matrix remodeling through TGF-beta1. Am J Physiol Heart Circ Physiol 310:H716–H724.  https://doi.org/10.1152/ajpheart.00309.2015 CrossRefPubMedGoogle Scholar
  70. 70.
    Meyer IS, Jungmann A, Dieterich C, Zhang M, Lasitschka F, Werkmeister S, Haas J, Muller OJ, Boutros M, Nahrendorf M, Katus HA, Hardt SE, Leuschner F (2017) The cardiac microenvironment uses non-canonical WNT signaling to activate monocytes after myocardial infarction. EMBO Mol Med 9:1279–1293.  https://doi.org/10.15252/emmm.201707565 CrossRefPubMedPubMedCentralGoogle Scholar
  71. 71.
    Minicucci MF, Azevedo PS, Polegato BF, Paiva SA, Zornoff LA (2011) Heart failure after myocardial infarction: clinical implications and treatment. Clin Cardiol 34:410–414.  https://doi.org/10.1002/clc.20922 CrossRefPubMedPubMedCentralGoogle Scholar
  72. 72.
    Mirotsou M, Zhang Z, Deb A, Zhang L, Gnecchi M, Noiseux N, Mu H, Pachori A, Dzau V (2007) Secreted frizzled related protein 2 (Sfrp2) is the key Akt-mesenchymal stem cell-released paracrine factor mediating myocardial survival and repair. Proc Natl Acad Sci USA 104:1643–1648.  https://doi.org/10.1073/pnas.0610024104 CrossRefPubMedPubMedCentralGoogle Scholar
  73. 73.
    Moon J, Zhou H, L-s Zhang, Tan W, Liu Y, Zhang S, Morlock LK, Bao X, Palecek SP, Feng JQ, Williams NS, Amatruda JF, Olson EN, Bassel-Duby R, Lum L (2017) Blockade to pathological remodeling of infarcted heart tissue using a porcupine antagonist. Proc Natl Acad Sci USA 114:1649–1654.  https://doi.org/10.1073/pnas.1621346114 CrossRefPubMedPubMedCentralGoogle Scholar
  74. 74.
    Morimoto H, Takahashi M (2007) Role of monocyte chemoattractant protein-1 in myocardial infarction. Int J Biomed Sci 3:159–167PubMedPubMedCentralGoogle Scholar
  75. 75.
    Morishita Y, Kobayashi K, Klyachko E, Jujo K, Maeda K, Losordo DW, Murohara T (2016) Wnt11 gene therapy with adeno-associated virus 9 improves recovery from myocardial infarction by modulating the inflammatory response. Sci Rep 6:21705.  https://doi.org/10.1038/srep21705 CrossRefPubMedPubMedCentralGoogle Scholar
  76. 76.
    Nahrendorf M, Pittet MJ, Swirski FK (2010) Monocytes: protagonists of infarct inflammation and repair after myocardial infarction. Circulation 121:2437–2445.  https://doi.org/10.1161/circulationaha.109.916346 CrossRefPubMedPubMedCentralGoogle Scholar
  77. 77.
    Nahrendorf M, Swirski FK, Aikawa E, Stangenberg L, Wurdinger T, Figueiredo JL, Libby P, Weissleder R, Pittet MJ (2007) The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. J Exp Med 204:3037–3047.  https://doi.org/10.1084/jem.20070885 CrossRefPubMedPubMedCentralGoogle Scholar
  78. 78.
    Nakagawa A, Naito AT, Sumida T, Nomura S, Shibamoto M, Higo T, Okada K, Sakai T, Hashimoto A, Kuramoto Y, Oka T, Lee JK, Harada M, Ueda K, Shiojima I, Limbourg FP, Adams RH, Noda T, Sakata Y, Akazawa H, Komuro I (2016) Activation of endothelial beta-catenin signaling induces heart failure. Sci Rep 6:25009.  https://doi.org/10.1038/srep25009 CrossRefPubMedPubMedCentralGoogle Scholar
  79. 79.
    Nakamura K, Sano S, Fuster JJ, Kikuchi R, Shimizu I, Ohshima K, Katanasaka Y, Ouchi N, Walsh K (2016) Secreted frizzled-related protein 5 diminishes cardiac inflammation and protects the heart from ischemia/reperfusion injury. J Biol Chem 291:2566–2575.  https://doi.org/10.1074/jbc.M115.693937 CrossRefPubMedGoogle Scholar
  80. 80.
    Niehrs C (2012) The complex world of WNT receptor signalling. Nat Rev Mol Cell Biol 13:767.  https://doi.org/10.1038/nrm3470 CrossRefPubMedPubMedCentralGoogle Scholar
  81. 81.
    Nishita M, Itsukushima S, Nomachi A, Endo M, Wang Z, Inaba D, Qiao S, Takada S, Kikuchi A, Minami Y (2010) Ror2/Frizzled complex mediates Wnt5a-induced AP-1 activation by regulating Dishevelled polymerization. Mol Cell Biol 30:3610–3619.  https://doi.org/10.1128/mcb.00177-10 CrossRefPubMedPubMedCentralGoogle Scholar
  82. 82.
    Nusse R, Clevers H (2017) Wnt/beta-catenin signaling, disease, and emerging therapeutic modalities. Cell 169:985–999.  https://doi.org/10.1016/j.cell.2017.05.016 CrossRefPubMedPubMedCentralGoogle Scholar
  83. 83.
    Nusse R, Varmus HE (1982) Many tumors induced by the mouse mammary tumor virus contain a provirus integrated in the same region of the host genome. Cell 31:99–109CrossRefPubMedCentralGoogle Scholar
  84. 84.
    Oerlemans MI, Goumans MJ, van Middelaar B, Clevers H, Doevendans PA, Sluijter JP (2010) Active Wnt signaling in response to cardiac injury. Basic Res Cardiol 105:631–641.  https://doi.org/10.1007/s00395-010-0100-9 CrossRefPubMedPubMedCentralGoogle Scholar
  85. 85.
    Ogawa S, Gerlach H, Esposito C, Pasagian-Macaulay A, Brett J, Stern D (1990) Hypoxia modulates the barrier and coagulant function of cultured bovine endothelium. Increased monolayer permeability and induction of procoagulant properties. J Clin Invest 85:1090–1098.  https://doi.org/10.1172/jci114540 CrossRefPubMedPubMedCentralGoogle Scholar
  86. 86.
    Oishi I, Suzuki H, Onishi N, Takada R, Kani S, Ohkawara B, Koshida I, Suzuki K, Yamada G, Schwabe GC, Mundlos S, Shibuya H, Takada S, Minami Y (2003) The receptor tyrosine kinase Ror2 is involved in non-canonical Wnt5a/JNK signalling pathway. Genes Cells 8:645–654CrossRefPubMedCentralGoogle Scholar
  87. 87.
    Onizuka T, Yuasa S, Kusumoto D, Shimoji K, Egashira T, Ohno Y, Kageyama T, Tanaka T, Hattori F, Fujita J, Ieda M, Kimura K, Makino S, Sano M, Kudo A, Fukuda K (2012) Wnt2 accelerates cardiac myocyte differentiation from ES-cell derived mesodermal cells via non-canonical pathway. J Mol Cell Cardiol 52:650–659.  https://doi.org/10.1016/j.yjmcc.2011.11.010 CrossRefPubMedPubMedCentralGoogle Scholar
  88. 88.
    Ozhan G, Weidinger G (2015) Wnt/β-catenin signaling in heart regeneration. Cell Regeneration 4(4):3.  https://doi.org/10.1186/s13619-015-0017-8 CrossRefPubMedPubMedCentralGoogle Scholar
  89. 89.
    Pai SG, Carneiro BA, Mota JM, Costa R, Leite CA, Barroso-Sousa R, Kaplan JB, Chae YK, Giles FJ (2017) Wnt/beta-catenin pathway: modulating anticancer immune response. J Hematol Oncol 10:101.  https://doi.org/10.1186/s13045-017-0471-6 CrossRefPubMedPubMedCentralGoogle Scholar
  90. 90.
    Paik DT, Rai M, Ryzhov S, Sanders LN, Aisagbonhi O, Funke MJ, Feoktistov I, Hatzopoulos AK (2015) Wnt10b gain-of-function improves cardiac repair by arteriole formation and attenuation of fibrosis. Circ Res 117:804–816.  https://doi.org/10.1161/circresaha.115.306886 CrossRefPubMedPubMedCentralGoogle Scholar
  91. 91.
    Palevski D, Levin-Kotler LP, Kain D, Naftali-Shani N, Landa N, Ben-Mordechai T, Konfino T, Holbova R, Molotski N, Rosin-Arbesfeld R, Lang RA, Leor J (2017) Loss of macrophage Wnt secretion improves remodeling and function after myocardial infarction in mice. J Am Heart Assoc.  https://doi.org/10.1161/jaha.116.004387 CrossRefPubMedPubMedCentralGoogle Scholar
  92. 92.
    Pan S, An L, Meng X, Li L, Ren F, Guan Y (2017) MgCl2 and ZnCl2 promote human umbilical vein endothelial cell migration and invasion and stimulate epithelial-mesenchymal transition via the Wnt/beta-catenin pathway. Exp Ther Med 14:4663–4670.  https://doi.org/10.3892/etm.2017.5144 CrossRefPubMedPubMedCentralGoogle Scholar
  93. 93.
    Pashirzad M, Shafiee M, Rahmani F, Behnam-Rassouli R, Hoseinkhani F, Ryzhikov M, Moradi Binabaj M, Parizadeh MR, Avan A, Hassanian SM (2017) Role of Wnt5a in the pathogenesis of inflammatory diseases. J Cell Physiol 232:1611–1616.  https://doi.org/10.1002/jcp.25687 CrossRefPubMedGoogle Scholar
  94. 94.
    Rao TP, Kuhl M (2010) An updated overview on Wnt signaling pathways: a prelude for more. Circ Res 106:1798–1806.  https://doi.org/10.1161/circresaha.110.219840 CrossRefPubMedGoogle Scholar
  95. 95.
    Reichsman F, Smith L, Cumberledge S (1996) Glycosaminoglycans can modulate extracellular localization of the wingless protein and promote signal transduction. J Cell Biol 135:819–827CrossRefGoogle Scholar
  96. 96.
    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.  https://doi.org/10.1007/s00395-017-0630-5 CrossRefPubMedPubMedCentralGoogle Scholar
  97. 97.
    Roarty K, Pfefferle AD, Creighton CJ, Perou CM, Rosen JM (2017) Ror2-mediated alternative Wnt signaling regulates cell fate and adhesion during mammary tumor progression. Oncogene 36:5958–5968.  https://doi.org/10.1038/onc.2017.206 CrossRefPubMedPubMedCentralGoogle Scholar
  98. 98.
    Sedgwick AE, D’Souza-Schorey C (2016) Wnt signaling in cell motility and invasion: drawing parallels between development and cancer. Cancers (Basel).  https://doi.org/10.3390/cancers8090080 CrossRefGoogle Scholar
  99. 99.
    Skaria T, Bachli E, Schoedon G (2017) Wnt5A/Ryk signaling critically affects barrier function in human vascular endothelial cells. Cell Adh Migr 11:24–38.  https://doi.org/10.1080/19336918.2016.1178449 CrossRefPubMedGoogle Scholar
  100. 100.
    Skaria T, Burgener J, Bachli E, Schoedon G (2016) IL-4 causes hyperpermeability of vascular endothelial cells through Wnt5A signaling. PLoS One 11:e0156002.  https://doi.org/10.1371/journal.pone.0156002 CrossRefPubMedPubMedCentralGoogle Scholar
  101. 101.
    Skelton Rhys J, Brady B, Khoja S, Sahoo D, Engel J, Arasaratnam D, Saleh Kholoud K, Abilez Oscar J, Zhao P, Stanley Edouard G, Elefanty Andrew G, Kwon M, Elliott David A, Ardehali R (2016) CD13 and ROR2 permit isolation of highly enriched cardiac mesoderm from differentiating human embryonic stem cells. Stem Cell Rep 6:95–108.  https://doi.org/10.1016/j.stemcr.2015.11.006 CrossRefGoogle Scholar
  102. 102.
    Slusarski DC, Yang-Snyder J, Busa WB, Moon RT (1997) Modulation of embryonic intracellular Ca2+ signaling by Wnt-5A. Dev Biol 182:114–120.  https://doi.org/10.1006/dbio.1996.8463 CrossRefPubMedGoogle Scholar
  103. 103.
    Soehnlein O, Zernecke A, Eriksson EE, Rothfuchs AG, Pham CT, Herwald H, Bidzhekov K, Rottenberg ME, Weber C, Lindbom L (2008) Neutrophil secretion products pave the way for inflammatory monocytes. Blood 112:1461–1471.  https://doi.org/10.1182/blood-2008-02-139634 CrossRefPubMedPubMedCentralGoogle Scholar
  104. 104.
    Tajbakhsh S, Borello U, Vivarelli E, Kelly R, Papkoff J, Duprez D, Buckingham M, Cossu G (1998) Differential activation of Myf5 and MyoD by different Wnts in explants of mouse paraxial mesoderm and the later activation of myogenesis in the absence of Myf5. Development 125:4155–4162PubMedGoogle Scholar
  105. 105.
    Tao J, Chen BD, Ma YT, Yang YN, Li XM, Ma X, Yu ZX, Liu F, Xiang Y, Chen Y (2015) FrzA gene protects cardiomyocytes from H2O2-induced oxidative stress through restraining the Wnt/Frizzled pathway. Lipids Health Dis 14:90.  https://doi.org/10.1186/s12944-015-0088-0 CrossRefPubMedPubMedCentralGoogle Scholar
  106. 106.
    Travers JG, Kamal FA, Robbins J, Yutzey KE, Blaxall BC (2016) Cardiac fibrosis. Fibroblast Awakens 118:1021–1040.  https://doi.org/10.1161/circresaha.115.306565 CrossRefGoogle Scholar
  107. 107.
    van Dijk EM, Menzen MH, Spanjer AI, Middag LD, Brandsma CA, Gosens R (2016) Noncanonical WNT-5B signaling induces inflammatory responses in human lung fibroblasts. Am J Physiol Lung Cell Mol Physiol 310:L1166–L1176.  https://doi.org/10.1152/ajplung.00226.2015 CrossRefPubMedPubMedCentralGoogle Scholar
  108. 108.
    Voloshanenko O, Schwartz U, Kranz D, Rauscher B, Linnebacher M, Augustin I, Boutros M (2018) beta-catenin-independent regulation of Wnt target genes by RoR2 and ATF2/ATF4 in colon cancer cells. Sci Rep 8:3178.  https://doi.org/10.1038/s41598-018-20641-5 CrossRefPubMedPubMedCentralGoogle Scholar
  109. 109.
    Wang Z, Cheng R, Lee K, Tyagi P, Ding L, Kompella UB, Chen J, Xu X, Ma JX (2015) Nanoparticle-mediated expression of a Wnt pathway inhibitor ameliorates ocular neovascularization. Arterioscler Thromb Vasc Biol 35:855–864.  https://doi.org/10.1161/atvbaha.114.304627 CrossRefPubMedPubMedCentralGoogle Scholar
  110. 110.
    Weirather J, Hofmann UD, Beyersdorf N, Ramos GC, Vogel B, Frey A, Ertl G, Kerkau T, Frantz S (2014) Foxp3 + CD4 + T cells improve healing after myocardial infarction by modulating monocyte/macrophage differentiation. Circ Res 115:55–67.  https://doi.org/10.1161/circresaha.115.303895 CrossRefPubMedPubMedCentralGoogle Scholar
  111. 111.
    World Health Organization (2017) World heart dayGoogle Scholar
  112. 112.
    Ye X, Lin J, Lin Z, Xue A, Li L, Zhao Z, Liu L, Shen Y, Cong B (2017) Axin1 up-regulated 1 accelerates stress-induced cardiomyocytes apoptosis through activating Wnt/beta-catenin signaling. Exp Cell Res 359:441–448.  https://doi.org/10.1016/j.yexcr.2017.08.027 CrossRefPubMedPubMedCentralGoogle Scholar
  113. 113.
    Zannad F (2017) Rising incidence of heart failure demands action. Lancet.  https://doi.org/10.1016/s0140-6736(17)32873-8 CrossRefPubMedPubMedCentralGoogle Scholar
  114. 114.
    Zhang J, Gill AJ, Issacs JD, Atmore B, Johns A, Delbridge LW, Lai R, McMullen TP (2012) The Wnt/beta-catenin pathway drives increased cyclin D1 levels in lymph node metastasis in papillary thyroid cancer. Hum Pathol 43:1044–1050.  https://doi.org/10.1016/j.humpath.2011.08.013 CrossRefPubMedPubMedCentralGoogle Scholar
  115. 115.
    Zhang M, Hagenmueller M, Riffel JH, Kreusser MM, Bernhold E, Fan J, Katus HA, Backs J, Hardt SE (2015) Calcium/calmodulin-dependent protein kinase II couples Wnt signaling with histone deacetylase 4 and mediates dishevelled-induced cardiomyopathy. Hypertension 65:335–344.  https://doi.org/10.1161/hypertensionaha.114.04467 CrossRefPubMedGoogle Scholar
  116. 116.
    Zouggari Y, Ait-Oufella H, Bonnin P, Simon T, Sage AP, Guerin C, Vilar J, Caligiuri G, Tsiantoulas D, Laurans L, Dumeau E, Kotti S, Bruneval P, Charo IF, Binder CJ, Danchin N, Tedgui A, Tedder TF, Silvestre JS, Mallat Z (2013) B lymphocytes trigger monocyte mobilization and impair heart function after acute myocardial infarction. Nat Med 19:1273–1280.  https://doi.org/10.1038/nm.3284 CrossRefPubMedPubMedCentralGoogle Scholar

Copyright information

© Springer-Verlag GmbH Germany, part of Springer Nature 2018

Authors and Affiliations

  1. 1.Department of Internal Medicine III, University Hospital HeidelbergUniversity of HeidelbergHeidelbergGermany
  2. 2.DZHK (German Centre for Cardiovascular Research)HeidelbergGermany

Personalised recommendations