Skip to main content
SpringerLink
Log in

Communication in the Heart: the Role of the Innate Immune System in Coordinating Cellular Responses to Ischemic Injury

  • Published:
Journal of Cardiovascular Translational Research Aims and scope Submit manuscript

Abstract

Ischemic cardiac injury is the leading cause of heart failure and mortality in the USA and is a major expense to health-care systems. Once the heart is injured, a highly dynamic and coordinated immune response is initiated, which is dependent on both resident and recruited leukocytes. The goal of the inflammatory response is to remove ischemic and necrotic material and to promote infarct healing. If this system is perturbed, the myocardium heals poorly, leading to significant left ventricular dysfunction. Understanding how inflammatory cells coordinate and interact with each other is required prior to designing therapeutic interventions that target pathological processes at play and leave untouched those processes that are protective. This review will discuss the intercellular cross talk between cells of the innate immune system following myocardial ischemic injury and how that response is coordinated over time.

This is a preview of subscription content, log in via an institution to check access.

Access this article

Log in via an institution

Price excludes VAT (USA)
Tax calculation will be finalised during checkout.

Instant access to the full article PDF.

Institutional subscriptions

Fig. 1
Fig. 2

Similar content being viewed by others

References

  1. Heidenreich, P. A., Trogdon, J. G., Khavjou, O. A., Butler, J., Dracup, K., Ezekowitz, M. D., Finkelstein, E. A., Hong, Y., Johnston, S. C., Khera, A., Lloyd-Jones, D. M., Nelson, S. A., Nichol, G., Orenstein, D., Wilson, P. W., & Woo, Y. J. (2011). Forecasting the future of cardiovascular disease in the United States: a policy statement from the American Heart Association. Circulation, 123, 933–944.

    Article  PubMed  Google Scholar 

  2. Gajarsa, J. J., & Kloner, R. A. (2011). Left ventricular remodeling in the post-infarction heart: a review of cellular, molecular mechanisms, and therapeutic modalities. Heart Failure Reviews, 16, 13–21.

    Article  PubMed  Google Scholar 

  3. Roe, M. T., Chen, A. Y., Cannon, C. P., Rao, S., Rumsfeld, J., Magid, D. J., Brindis, R., Klein, L. W., Gibler, W. B., Ohman, E. M., & Peterson, E. D. (2009). Temporal changes in the use of drug-eluting stents for patients with non-ST-segment-elevation myocardial infarction undergoing percutaneous coronary intervention from 2006 to 2008: results from the can rapid risk stratification of unstable angina patients suppress adverse outcomes with early implementation of the ACC/AHA guidelines (CRUSADE) and acute coronary treatment and intervention outcomes network-get with the guidelines (ACTION-GWTG) registries. Circulation. Cardiovascular Quality and Outcomes, 2, 414–420.

    Article  PubMed  Google Scholar 

  4. Kaczorowski, D. J., Tsung, A., & Billiar, T. R. (2009). Innate immune mechanisms in ischemia/reperfusion. Frontiers in Bioscience (Elite Edition), 1, 91–98.

    Google Scholar 

  5. Gallucci, S., & Matzinger, P. (2001). Danger signals: SOS to the immune system. Current Opinion in Immunology, 13, 114–119.

    Article  PubMed  CAS  Google Scholar 

  6. Ionita, M. G., Arslan, F., de Kleijn, D. P., & Pasterkamp, G. (2010). Endogenous inflammatory molecules engage Toll-like receptors in cardiovascular disease. Journal of Innate Immunity, 2, 307–315.

    Article  PubMed  CAS  Google Scholar 

  7. Frangogiannis, N. G., Lindsey, M. L., Michael, L. H., Youker, K. A., Bressler, R. B., Mendoza, L. H., Spengler, R. N., Smith, C. W., & Entman, M. L. (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.

    Article  PubMed  CAS  Google Scholar 

  8. Chakraborti, T., Mandal, A., Mandal, M., Das, S., & Chakraborti, S. (2000). Complement activation in heart diseases. Role of oxidants. Cell Signalling, 12, 607–617.

    Article  PubMed  CAS  Google Scholar 

  9. Foreman, K. E., Glovsky, M. M., Warner, R. L., Horvath, S. J., & Ward, P. A. (1996). Comparative effect of C3a and C5a on adhesion molecule expression on neutrophils and endothelial cells. Inflammation, 20, 1–9.

    Article  PubMed  CAS  Google Scholar 

  10. Tyagi, S., Klickstein, L. B., & Nicholson-Weller, A. (2000). C5a-stimulated human neutrophils use a subset of beta2 integrins to support the adhesion-dependent phase of superoxide production. Journal of Leukocyte Biology, 68, 679–686.

    PubMed  CAS  Google Scholar 

  11. Engels, W., Reiters, P. H., Daemen, M. J., Smits, J. F., & van der Vusse, G. J. (1995). Transmural changes in mast cell density in rat heart after infarct induction in vivo. The Journal of Pathology, 177, 423–429.

    Article  PubMed  CAS  Google Scholar 

  12. Bhattacharya, K., Farwell, K., Huang, M., Kempuraj, D., Donelan, J., Papaliodis, D., Vasiadi, M., & Theoharides, T. C. (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. International Journal of Immunopathology and Pharmacology, 20, 69–74.

    PubMed  CAS  Google Scholar 

  13. Ayach, B. B., Yoshimitsu, M., Dawood, F., Sun, M., Arab, S., Chen, M., Higuchi, K., Siatskas, C., Lee, P., Lim, H., Zhang, J., Cukerman, E., Stanford, W. L., Medin, J. A., & Liu, P. P. (2006). Stem cell factor receptor induces progenitor and natural killer cell-mediated cardiac survival and repair after myocardial infarction. Proceedings of the National Academy of Sciences of the United States of America, 103, 2304–2309.

    Article  PubMed  CAS  Google Scholar 

  14. Waskow, C., Paul, S., Haller, C., Gassmann, M., & Rodewald, H. R. (2002). Viable c-Kit(W/W) mutants reveal pivotal role for c-kit in the maintenance of lymphopoiesis. Immunity, 17, 277–288.

    Article  PubMed  CAS  Google Scholar 

  15. Dreyer, W. J., Michael, L. H., Nguyen, T., Smith, C. W., Anderson, D. C., Entman, M. L., & Rossen, R. D. (1992). Kinetics of C5a release in cardiac lymph of dogs experiencing coronary artery ischemia-reperfusion injury. Circulation Research, 71, 1518–1524.

    Article  PubMed  CAS  Google Scholar 

  16. Entman, M. L., Youker, K., Shappell, S. B., Siegel, C., Rothlein, R., Dreyer, W. J., Schmalstieg, F. C., & Smith, C. W. (1990). Neutrophil adherence to isolated adult canine myocytes. Evidence for a CD18-dependent mechanism. Journal of Clinical Investigation, 85, 1497–1506.

    Article  PubMed  CAS  Google Scholar 

  17. Gwechenberger, M., Mendoza, L. H., Youker, K. A., Frangogiannis, N. G., Smith, C. W., Michael, L. H., & Entman, M. L. (1999). Cardiac myocytes produce interleukin-6 in culture and in viable border zone of reperfused infarctions. Circulation, 99, 546–551.

    Article  PubMed  CAS  Google Scholar 

  18. Youker, K., Smith, C. W., Anderson, D. C., Miller, D., Michael, L. H., Rossen, R. D., & Entman, M. L. (1992). Neutrophil adherence to isolated adult cardiac myocytes. Induction by cardiac lymph collected during ischemia and reperfusion. The Journal of Clinical Investigation, 89, 602–609.

    Article  PubMed  CAS  Google Scholar 

  19. Entman, M. L., Youker, K., Shoji, T., Kukielka, G., Shappell, S. B., Taylor, A. A., & Smith, C. W. (1992). Neutrophil induced oxidative injury of cardiac myocytes. A compartmented system requiring CD11b/CD18-ICAM-1 adherence. Journal of Clinical Investigation, 90, 1335–1345.

    Article  PubMed  CAS  Google Scholar 

  20. Kawakami, R., Saito, Y., Kishimoto, I., Harada, M., Kuwahara, K., Takahashi, N., Nakagawa, Y., Nakanishi, M., Tanimoto, K., Usami, S., Yasuno, S., Kinoshita, H., Chusho, H., Tamura, N., Ogawa, Y., & Nakao, K. (2004). Overexpression of brain natriuretic peptide facilitates neutrophil infiltration and cardiac matrix metalloproteinase-9 expression after acute myocardial infarction. Circulation, 110, 3306–3312.

    Article  PubMed  CAS  Google Scholar 

  21. Romson, J. L., Hook, B. G., Kunkel, S. L., Abrams, G. D., Schork, M. A., & Lucchesi, B. R. (1983). Reduction of the extent of ischemic myocardial injury by neutrophil depletion in the dog. Circulation, 67, 1016–1023.

    Article  PubMed  CAS  Google Scholar 

  22. Jolly, S. R., Kane, W. J., Hook, B. G., Abrams, G. D., Kunkel, S. L., & Lucchesi, B. R. (1986). Reduction of myocardial infarct size by neutrophil depletion: effect of duration of occlusion. American Heart Journal, 112, 682–690.

    Article  PubMed  CAS  Google Scholar 

  23. McDonald, B., Pittman, K., Menezes, G. B., Hirota, S. A., Slaba, I., Waterhouse, C. C., Beck, P. L., Muruve, D. A., & Kubes, P. (2010). Intravascular danger signals guide neutrophils to sites of sterile inflammation. Science, 330, 362–366.

    Article  PubMed  CAS  Google Scholar 

  24. Murphy, P. M., Ozcelik, T., Kenney, R. T., Tiffany, H. L., McDermott, D., & Francke, U. (1992). A structural homologue of the N-formyl peptide receptor. Characterization and chromosome mapping of a peptide chemoattractant receptor family. Journal of Biological Chemistry, 267, 7637–7643.

    PubMed  CAS  Google Scholar 

  25. Oka, T., Hikoso, S., Yamaguchi, O., Taneike, M., Takeda, T., Tamai, T., Oyabu, J., Murakawa, T., Nakayama, H., Nishida, K., Akira, S., Yamamoto, A., Komuro, I., & Otsu, K. (2012). Mitochondrial DNA that escapes from autophagy causes inflammation and heart failure. Nature, 485, 251–255.

    Article  PubMed  CAS  Google Scholar 

  26. Zhang, Q., Raoof, M., Chen, Y., Sumi, Y., Sursal, T., Junger, W., Brohi, K., Itagaki, K., & Hauser, C. J. (2010). Circulating mitochondrial DAMPs cause inflammatory responses to injury. Nature, 464, 104–107.

    Article  PubMed  CAS  Google Scholar 

  27. Nahrendorf, M., Swirski, F. K., Aikawa, E., Stangenberg, L., Wurdinger, T., Figueiredo, J. L., Libby, P., Weissleder, R., & Pittet, M. J. (2007). The healing myocardium sequentially mobilizes two monocyte subsets with divergent and complementary functions. The Journal of Experimental Medicine, 204, 3037–3047.

    Article  PubMed  CAS  Google Scholar 

  28. Nossuli, T. O., Lakshminarayanan, V., Baumgarten, G., Taffet, G. E., Ballantyne, C. M., Michael, L. H., & Entman, M. L. (2000). A chronic mouse model of myocardial ischemia-reperfusion: essential in cytokine studies. American Journal of Physiology. Heart and Circulatory Physiology, 278, H1049–H1055.

    PubMed  CAS  Google Scholar 

  29. Tsujioka, H., Imanishi, T., Ikejima, H., Kuroi, A., Takarada, S., Tanimoto, T., Kitabata, H., Okochi, K., Arita, Y., Ishibashi, K., Komukai, K., Kataiwa, H., Nakamura, N., Hirata, K., Tanaka, A., & Akasaka, T. (2009). Impact of heterogeneity of human peripheral blood monocyte subsets on myocardial salvage in patients with primary acute myocardial infarction. Journal of the American College of Cardiology, 54, 130–138.

    Article  PubMed  Google Scholar 

  30. Swirski, F. K., Nahrendorf, M., Etzrodt, M., Wildgruber, M., Cortez-Retamozo, V., Panizzi, P., Figueiredo, J. L., Kohler, R. H., Chudnovskiy, A., Waterman, P., Aikawa, E., Mempel, T. R., Libby, P., Weissleder, R., & Pittet, M. J. (2009). Identification of splenic reservoir monocytes and their deployment to inflammatory sites. Science, 325, 612–616.

    Article  PubMed  CAS  Google Scholar 

  31. Leuschner, F., Rauch, P. J., Ueno, T., Gorbatov, R., Marinelli, B., Lee, W. W., Dutta, P., Wei, Y., Robbins, C., Iwamoto, Y., Sena, B., Chudnovskiy, A., Panizzi, P., Keliher, E., Higgins, J. M., Libby, P., Moskowitz, M. A., Pittet, M. J., Swirski, F. K., Weissleder, R., & Nahrendorf, M. (2012). Rapid monocyte kinetics in acute myocardial infarction are sustained by extramedullary monocytopoiesis. The Journal of Experimental Medicine, 209, 123–137.

    Article  PubMed  CAS  Google Scholar 

  32. Hanna, R. N., Carlin, L. M., Hubbeling, H. G., Nackiewicz, D., Green, A. M., Punt, J. A., Geissmann, F., & Hedrick, C. C. (2011). The transcription factor NR4A1 (Nur77) controls bone marrow differentiation and the survival of Ly6C − monocytes. Nature Immunology, 12, 778–785.

    Article  PubMed  CAS  Google Scholar 

  33. Panizzi, P., Swirski, F. K., Figueiredo, J. L., Waterman, P., Sosnovik, D. E., Aikawa, E., Libby, P., Pittet, M., Weissleder, R., & Nahrendorf, M. (2010). Impaired infarct healing in atherosclerotic mice with Ly-6C(hi) monocytosis. Journal of the American College of Cardiology, 55, 1629–1638.

    Article  PubMed  Google Scholar 

  34. Swirski, F. K., Libby, P., Aikawa, E., Alcaide, P., Luscinskas, F. W., Weissleder, R., & Pittet, M. J. (2007). Ly-6Chi monocytes dominate hypercholesterolemia-associated monocytosis and give rise to macrophages in atheromata. The Journal of Clinical Investigation, 117, 195–205.

    Article  PubMed  CAS  Google Scholar 

  35. Capoccia, B. J., Gregory, A. D., & Link, D. C. (2008). Recruitment of the inflammatory subset of monocytes to sites of ischemia induces angiogenesis in a monocyte chemoattractant protein-1-dependent fashion. Journal of Leukocyte Biology, 84, 760–768.

    Article  PubMed  CAS  Google Scholar 

  36. Kreisel, D., Nava, R. G., Li, W., Zinselmeyer, B. H., Wang, B., Lai, J., Pless, R., Gelman, A. E., Krupnick, A. S., & Miller, M. J. (2010). In vivo two-photon imaging reveals monocyte-dependent neutrophil extravasation during pulmonary inflammation. Proceedings of the National Academy of Sciences of the United States of America, 107, 18073–18078.

    Article  PubMed  CAS  Google Scholar 

  37. Soehnlein, O., Lindbom, L., & Weber, C. (2009). Mechanisms underlying neutrophil-mediated monocyte recruitment. Blood, 114, 4613–4623.

    Article  PubMed  CAS  Google Scholar 

  38. Jenkins, S. J., Ruckerl, D., Cook, P. C., Jones, L. H., Finkelman, F. D., van Rooijen, N., MacDonald, A. S., & Allen, J. E. (2011). Local macrophage proliferation, rather than recruitment from the blood, is a signature of TH2 inflammation. Science, 332, 1284–1288.

    Article  PubMed  CAS  Google Scholar 

  39. Fadok, V. A., Bratton, D. L., Konowal, A., Freed, P. W., Westcott, J. Y., & Henson, P. M. (1998). Macrophages that have ingested apoptotic cells in vitro inhibit proinflammatory cytokine production through autocrine/paracrine mechanisms involving TGF-beta, PGE2, and PAF. The Journal of Clinical Investigation, 101, 890–898.

    Article  PubMed  CAS  Google Scholar 

  40. Voll, R. E., Herrmann, M., Roth, E. A., Stach, C., Kalden, J. R., & Girkontaite, I. (1997). Immunosuppressive effects of apoptotic cells. Nature, 390, 350–351.

    Article  PubMed  CAS  Google Scholar 

  41. Stark, M. A., Huo, Y., Burcin, T. L., Morris, M. A., Olson, T. S., & Ley, K. (2005). Phagocytosis of apoptotic neutrophils regulates granulopoiesis via IL-23 and IL-17. Immunity, 22, 285–294.

    Article  PubMed  CAS  Google Scholar 

  42. Kobayashi, S. D., Voyich, J. M., Braughton, K. R., & DeLeo, F. R. (2003). Down-regulation of proinflammatory capacity during apoptosis in human polymorphonuclear leukocytes. Journal of Immunology, 170, 3357–3368.

    CAS  Google Scholar 

  43. Kobayashi, S. D., Voyich, J. M., Somerville, G. A., Braughton, K. R., Malech, H. L., Musser, J. M., & DeLeo, F. R. (2003). An apoptosis-differentiation program in human polymorphonuclear leukocytes facilitates resolution of inflammation. Journal of Leukocyte Biology, 73, 315–322.

    Article  PubMed  CAS  Google Scholar 

  44. Jonsson, H., Allen, P., & Peng, S. L. (2005). Inflammatory arthritis requires Foxo3a to prevent Fas ligand-induced neutrophil apoptosis. Nature Medicine, 11, 666–671.

    Article  PubMed  CAS  Google Scholar 

  45. Tan, W., Huang, W., Gu, X., Zhong, Q., Liu, B., & Schwarzenberger, P. (2008). IL-17F/IL-17R interaction stimulates granulopoiesis in mice. Experimental Hematology, 36, 1417–1427.

    Article  PubMed  CAS  Google Scholar 

  46. Schwarzenberger, P., Huang, W., Ye, P., Oliver, P., Manuel, M., Zhang, Z., Bagby, G., Nelson, S., & Kolls, J. K. (2000). Requirement of endogenous stem cell factor and granulocyte-colony-stimulating factor for IL-17-mediated granulopoiesis. Journal of Immunology, 164, 4783–4789.

    CAS  Google Scholar 

  47. Leuschner, F., Panizzi, P., Chico-Calero, I., Lee, W. W., Ueno, T., Cortez-Retamozo, V., Waterman, P., Gorbatov, R., Marinelli, B., Iwamoto, Y., Chudnovskiy, A., Figueiredo, J. L., Sosnovik, D. E., Pittet, M. J., Swirski, F. K., Weissleder, R., & Nahrendorf, M. (2010). Angiotensin-converting enzyme inhibition prevents the release of monocytes from their splenic reservoir in mice with myocardial infarction. Circulation Research, 107, 1364–1373.

    Article  PubMed  CAS  Google Scholar 

  48. Dewald, O., Zymek, P., Winkelmann, K., Koerting, A., Ren, G., bou-Khamis, T., Michael, L. H., Rollins, B. J., Entman, M. L., & Frangogiannis, N. G. (2005). CCL2/monocyte chemoattractant protein-1 regulates inflammatory responses critical to healing myocardial infarcts. Circulation Research, 96, 881–889.

    Article  PubMed  CAS  Google Scholar 

  49. van Amerongen, M. J., Harmsen, M. C., van Rooijen, N., Petersen, A. H., & van Luyn, M. J. (2007). Macrophage depletion impairs wound healing and increases left ventricular remodeling after myocardial injury in mice. American Journal of Pathology, 170, 818–829.

    Article  PubMed  Google Scholar 

  50. Anzai, A., Anzai, T., Nagai, S., Maekawa, Y., Naito, K., Kaneko, H., Sugano, Y., Takahashi, T., Abe, H., Mochizuki, S., Sano, M., Yoshikawa, T., Okada, Y., Koyasu, S., Ogawa, S., & Fukuda, K. (2012). Regulatory role of dendritic cells in postinfarction healing and left ventricular remodeling. Circulation, 125, 1234–1245.

    Article  PubMed  Google Scholar 

  51. Sutton, C. E., Lalor, S. J., Sweeney, C. M., Brereton, C. F., Lavelle, E. C., & Mills, K. H. (2009). Interleukin-1 and IL-23 induce innate IL-17 production from gammadelta T cells, amplifying Th17 responses and autoimmunity. Immunity, 31, 331–341.

    Article  PubMed  CAS  Google Scholar 

  52. Martin, B., Hirota, K., Cua, D. J., Stockinger, B., & Veldhoen, M. (2009). Interleukin-17-producing gammadelta T cells selectively expand in response to pathogen products and environmental signals. Immunity, 31, 321–330.

    Article  PubMed  CAS  Google Scholar 

  53. Liao, Y. H., Xia, N., Zhou, S. F., Tang, T. T., Yan, X. X., Lv, B. J., Nie, S. F., Wang, J., Iwakura, Y., Xiao, H., Yuan, J., Jevallee, H., Wei, F., Shi, G. P., & Cheng, X. (2012). Interleukin-17A contributes to myocardial ischemia/reperfusion injury by regulating cardiomyocyte apoptosis and neutrophil infiltration. Journal of the American College of Cardiology, 59, 420–429.

    Article  PubMed  CAS  Google Scholar 

  54. 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.

    Article  PubMed  CAS  Google Scholar 

  55. Matsumoto, K., Ogawa, M., Suzuki, J., Hirata, Y., Nagai, R., & Isobe, M. (2011). Regulatory T lymphocytes attenuate myocardial infarction-induced ventricular remodeling in mice. International Heart Journal, 52, 382–387.

    Article  PubMed  CAS  Google Scholar 

  56. Dobaczewski, M., Xia, Y., Bujak, M., Gonzalez-Quesada, C., & Frangogiannis, N. G. (2010). CCR5 signaling suppresses inflammation and reduces adverse remodeling of the infarcted heart, mediating recruitment of regulatory T cells. American Journal of Pathology, 176, 2177–2187.

    Article  PubMed  CAS  Google Scholar 

  57. Yang, Z., Day, Y. J., Toufektsian, M. C., Xu, Y., Ramos, S. I., Marshall, M. A., French, B. A., & Linden, J. (2006). Myocardial infarct-sparing effect of adenosine A2A receptor activation is due to its action on CD4+ T lymphocytes. Circulation, 114, 2056–2064.

    Article  PubMed  CAS  Google Scholar 

  58. Clynes, R. (2007). Protective mechanisms of IVIG. Current Opinion in Immunology, 19, 646–651.

    Article  PubMed  CAS  Google Scholar 

  59. Curato, C., Slavic, S., Dong, J., Skorska, A., tarche-Xifro, W., Miteva, K., Kaschina, E., Thiel, A., Imboden, H., Wang, J., Steckelings, U., Steinhoff, G., Unger, T., & Li, J. (2010). Identification of noncytotoxic and IL-10-producing CD8+AT2R+ T cell population in response to ischemic heart injury. Journal of Immunology, 185, 6286–6293.

    Article  CAS  Google Scholar 

  60. Kaschina, E., Grzesiak, A., Li, J., Foryst-Ludwig, A., Timm, M., Rompe, F., Sommerfeld, M., Kemnitz, U. R., Curato, C., Namsolleck, P., Tschope, C., Hallberg, A., Alterman, M., Hucko, T., Paetsch, I., Dietrich, T., Schnackenburg, B., Graf, K., Dahlof, B., Kintscher, U., Unger, T., & Steckelings, U. M. (2008). Angiotensin II type 2 receptor stimulation: a novel option of therapeutic interference with the renin-angiotensin system in myocardial infarction? Circulation, 118, 2523–2532.

    Article  PubMed  CAS  Google Scholar 

  61. Cohn, J. N., & Tognoni, G. (2001). A randomized trial of the angiotensin-receptor blocker valsartan in chronic heart failure. The New England Journal of Medicine, 345, 1667–1675.

    Article  PubMed  CAS  Google Scholar 

  62. Dickstein, K., & Kjekshus, J. (2002). Effects of losartan and captopril on mortality and morbidity in high-risk patients after acute myocardial infarction: the OPTIMAAL randomised trial. Optimal trial in myocardial infarction with angiotensin II antagonist losartan. Lancet, 360, 752–760.

    Article  PubMed  CAS  Google Scholar 

  63. Mehta, P. K., & Griendling, K. K. (2007). Angiotensin II cell signaling: physiological and pathological effects in the cardiovascular system. American Journal of Physiology. Cell Physiology, 292, C82–C97.

    Article  PubMed  CAS  Google Scholar 

  64. Bouchentouf, M., Forner, K. A., Cuerquis, J., Michaud, V., Zheng, J., Paradis, P., Schiffrin, E. L., & Galipeau, J. (2010). Induction of cardiac angiogenesis requires killer cell lectin-like receptor 1 and alpha4beta7 integrin expression by NK cells. Journal of Immunology, 185, 7014–7025.

    Article  CAS  Google Scholar 

  65. Li, W., Nava, R. G., Bribriesco, A. C., Zinselmeyer, B. H., Spahn, J. H., Gelman, A. E., Krupnick, A. S., Miller, M. J., & Kreisel, D. (2012). Intravital 2-photon imaging of leukocyte trafficking in beating heart. The Journal of Clinical Investigation, 122, 2499–2508.

    Article  PubMed  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Center for Cardiovascular Research., Division of Cardiology, Department of Medicine, Washington University School of Medicine, 660 South Euclid Avenue, St. Louis, MO, 63110-1093, USA

    Slava Epelman & Douglas L. Mann

Authors
  1. Slava Epelman
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Douglas L. Mann
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Slava Epelman.

Rights and permissions

Reprints and permissions

About this article

Cite this article

Epelman, S., Mann, D.L. Communication in the Heart: the Role of the Innate Immune System in Coordinating Cellular Responses to Ischemic Injury. J. of Cardiovasc. Trans. Res. 5, 827–836 (2012). https://doi.org/10.1007/s12265-012-9410-7

Download citation

  • Received:

  • Accepted:

  • Published:

  • Issue Date:

  • DOI: https://doi.org/10.1007/s12265-012-9410-7

Keywords

Search

Navigation