Journal of Cardiac Failure
Volume 16, Issue 9 , Pages 777-785 , September 2010

Effects of ACE2 Inhibition in the Post-Myocardial Infarction Heart

  • Myung-A. Kim, MD

      Affiliations

    • Seoul National University, Seoul, Korea
    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • ,
  • Dongheon Yang, MD, PhD

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • Department of Internal Medicine, Kyungpook National University School of Medicine, Daegu, South Korea
    • ,
  • Keisuke Kida, MD, PhD

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • St. Marianna University School of Medicine, Kawaski, Japan
    • ,
  • Natalia Molotkova, PhD

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • ,
  • Seon Ju Yeo, PhD

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • ,
  • Nissi Varki, NM

      Affiliations

    • Department of Pathology, University of California, San Diego
    • ,
  • Michikado Iwata, MD

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • ,
  • Nancy D. Dalton, RDCS

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • ,
  • Kirk L. Peterson, MD

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • ,
  • Wolf-Eberhard Siems, PhD

      Affiliations

    • Leibniz-Institute for Molecular Pharmacology, Berlin, Germany
    • ,
  • Thomas Walther, PhD

      Affiliations

    • Centre for Biomedical Research, Hull York Medical School, Hull, United Kingdom
    • Department of Experimental Cardiology, Excellence Cluster Cardio-Pulmonary System, Justus-Liebig-Universität Giessen, Giessen, Germany
    • ,
  • Randy T. Cowling, PhD

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • ,
  • John Kjekshus, MD, PhD

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • Division of Cardiology, University of Oslo, Norway
    • ,
  • Barry Greenberg, MD

      Affiliations

    • Division of Cardiology, Kyungpook National University School of Medicine, Daegu, South Korea
    • Corresponding Author InformationReprint requests: Barry Greenberg, MD, Professor of Medicine, Director, Advanced Heart Failure Treatment Program, University of California at San Diego Medical Center, 200 West Arbor Street, San Diego, CA 92103-8411, Tel: (619) 543-7751; Fax: (619) 543-5543.

Received 6 September 2009 ,Revised 11 April 2010 ,Accepted 12 April 2010.

References 

  1. Serneri GG, Boddi M, Cecioni I, Vanni S, Coppo M, Papa ML, et al. Cardiac angiotensin II formation in the clinical course of heart failure and its relationship with left ventricular function. Circ Res. 2001;88:961–968
  2. Sharpe N. Cardiac remodeling in congestive heart failure. In:  Hosenpud JD,  Greenberg BH editor. Congestive heart failure. Second ed. Philadelphia: Lippincott Williams & Wilkins; 2000;p. 101–115
  3. Weber KT. Extracellular matrix remodeling in heart failure: a role for de novo angiotensin II generation. Circulation. 1997;96:4065–4082
  4. Dostal DE, Baker KM. The cardiac renin-angiotensin system: conceptual, or a regulator of cardiac function?. Circ Res. 1999;85:643–650
  5. Kim NN, Villarreal FJ, Printz MP, Lee AA, Dillmann WH. Trophic effects of angiotensin II on neonatal rat cardiac myocytes are mediated by cardiac fibroblasts. Am J Physiol. 1995;269:E426–E437
  6. Kim S, Ohta K, Hamaguchi A, Yukimura T, Miura K, Iwao H. Angiotensin II induces cardiac phenotypic modulation and remodeling in vivo in rats. Hypertension. 1995;25:1252–1259
  7. Pfeffer JM, Pfeffer MA, Fletcher PJ, Braunwald E. Progressive ventricular remodeling in rat with myocardial infarction. Am J Physiol. 1991;260:H1406–H1414
  8. Weber KT, Sun Y. Remodeling of the cardiac interstitium in ischemic cardiomyopathy. In:  Hosenpud JD,  Greenberg BH editor. Congestive heart failure. Second ed. Philadelphia: Lippincott Williams & Wilkins; 2000;p. 117–136
  9. Pfeffer JM, Pfeffer MA, Braunwald E. Influence of chronic captopril therapy on the infarcted left ventricle of the rat. Circ Res. 1985;57:84–95
  10. Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ, Cuddy TE, et al. Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. The SAVE Investigators [see comments]. N Engl J Med. 1992;327:669–677
  11. Greenberg B, Quinones MA, Koilpillai C, Limacher M, Shindler D, Benedict C, et al. Effects of long-term enalapril therapy on cardiac structure and function in patients with left ventricular dysfunction. Results of the SOLVD echocardiography substudy. Circulation. 1995;91:2573–2581
  12. Burrell LM, Johnston CI, Tikellis C, Cooper ME. ACE2, a new regulator of the renin-angiotensin system. Trends Endocrinol Metab. 2004;15:166–169
  13. Donoghue M, Hsieh F, Baronas E, Godbout K, Gosselin M, Stagliano N, et al. A novel angiotensin-converting enzyme-related carboxypeptidase (ACE2) converts angiotensin I to angiotensin 1-9. Circ Res. 2000;87:E1–E9
  14. Crackower MA, Sarao R, Oudit GY, Yagil C, Kozieradzki I, Scanga SE, et al. Angiotensin-converting enzyme 2 is an essential regulator of heart function. Nature. 2002;417:822–828
  15. Tipnis SR, Hooper NM, Hyde R, Karran E, Christie G, Turner AJ. A human homolog of angiotensin-converting enzyme–cloning and functional expression as a captopril-insensitive carboxypeptidase. J Biol Chem. 2000;275:33238–33243
  16. Harmer D, Gilbert M, Borman R, Clark KL. Quantitative mRNA expression profiling of ACE 2, a novel homologue of angiotensin converting enzyme. FEBS Lett. 2002;532:107–110
  17. Vickers C, Hales P, Kaushik V, Dick L, Gavin J, Tang J, et al. Hydrolysis of biological peptides by human angiotensin-converting enzyme-related carboxypeptidase. J Biol Chem. 2002;277:14838–14843
  18. Zisman LS, Meixell GE, Bristow MR, Canver CC. Angiotensin-(1-7) formation in the intact human heart: in vivo dependence on angiotensin II as substrate. Circulation. 2003;108:1679–1681
  19. Brosnihan KB, Li P, Ferrario CM. Angiotensin-(1-7) dilates canine coronary arteries through kinins and nitric oxide. Hypertension. 1996;27:523–528
  20. Freeman EJ, Chisolm GM, Ferrario CM, Tallant EA. Angiotensin-(1-7) inhibits vascular smooth muscle cell growth. Hypertension. 1996;28:104–108
  21. Iwata M, Cowling RT, Gurantz D, Moore C, Zhang S, Yuan JX, et al. Angiotensin-(1-7) binds to specific receptors on cardiac fibroblasts to initiate antifibrotic and antitrophic effects. Am J Physiol Heart Circ Physiol. 2005;289:H2356–H2363
  22. Strawn WB, Ferrario CM, Tallant EA. Angiotensin-(1-7) reduces smooth muscle growth after vascular injury. Hypertension. 1999;33:207–211
  23. Tallant EA, Ferrario CM, Gallagher PE. Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor. Am J Physiol Heart Circ Physiol. 2005;289:H1560–H1566
  24. Gurley SB, Allred A, Le TH, Griffiths R, Mao L, Philip N, et al. Altered blood pressure responses and normal cardiac phenotype in ACE2-null mice. J Clin Invest. 2006;116:2218–2225
  25. Ambrose J, Pribnow DG, Giraud GD, Perkins KD, Muldoon L, Greenberg BH. Angiotensin type 1 receptor antagonism with irbesartan inhibits ventricular hypertrophy and improves diastolic function in the remodeling post-myocardial infarction ventricle. J Cardiovasc Pharmacol. 1999;33:433–439
  26. Gurantz D, Cowling RT, Varki N, Frikovsky E, Moore CD, Greenberg BH. 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. 2005;38:505–515
  27. Dales NA, Gould AE, Brown JA, Calderwood EF, Guan B, Minor CA, et al. Substrate-based design of the first class of angiotensin-converting enzyme-related carboxypeptidase (ACE2) inhibitors. J Am Chem Soc. 2002;124:11852–11853
  28. Pfeffer MA, Braunwald E. Ventricular remodeling after myocardial infarction. Experimental observations and clinical implications. Circulation. 1990;81:1161–1172
  29. Pfeffer MA, Lamas GA, Vaughan DE, Parisi AF, Braunwald E. Effect of captopril on progressive ventricular dilatation after anterior myocardial infarction. N Engl J Med. 1988;319:80–86
  30. Kober L, Torp-Pedersen C, Carlsen JE, Bagger H, Eliasen P, Lyngborg K, et al. A clinical trial of the angiotensin-converting-enzyme inhibitor trandolapril in patients with left ventricular dysfunction after myocardial infarction. Trandolapril Cardiac Evaluation (TRACE) Study Group. N Engl J Med. 1995;333:1670–1676
  31. Jin H, Yang R, Awad TA, Wang F, Li W, Williams SP, et al. Effects of early angiotensin-converting enzyme inhibition on cardiac gene expression after acute myocardial infarction. Circulation. 2001;103:736–742
  32. Mankad S, d'Amato TA, Reichek N, McGregor WE, Lin J, Singh D, et al. Combined angiotensin II receptor antagonism and angiotensin-converting enzyme inhibition further attenuates postinfarction left ventricular remodeling. Circulation. 2001;103:2845–2850
  33. Zhu Z, Zhong J, Zhu S, Liu D, Van Der GM, Tepel M. Angiotensin-(1-7) inhibits angiotensin II-induced signal transduction. J Cardiovasc Pharmacol. 2002;40:693–700
  34. Kajstura J, Cheng W, Reiss K, Clark WA, Sonnenblick EH, Krajewski S, et al. Apoptotic and necrotic myocyte cell deaths are independent contributing variables of infarct size in rats. Lab Invest. 1996;74:86–107
  35. Beltrami AP, Barlucchi L, Torella D, Baker M, Limana F, Chimenti S, et al. Adult cardiac stem cells are multipotent and support myocardial regeneration. Cell. 2003;114:763–776
  36. Guan K, Hasenfuss G. Do stem cells in the heart truly differentiate into cardiomyocytes?. J Mol Cell Cardiol. 2007;43:377–387
  37. Orlic D, Kajstura J, Chimenti S, Limana F, Jakoniuk I, Quaini F, et al. Mobilized bone marrow cells repair the infarcted heart, improving function and survival. Proc Natl Acad Sci U S A. 2001;98:10344–10349
  38. Zisman LS, Keller RS, Weaver B, Lin Q, Speth R, Bristow MR, et al. Increased angiotensin-(1-7)-forming activity in failing human heart ventricles: evidence for upregulation of the angiotensin-converting enzyme Homologue ACE2. Circulation. 2003;108:1707–1712
  39. Lemos VS, Silva DM, Walther T, Alenina N, Bader M, Santos RA. The endothelium-dependent vasodilator effect of the nonpeptide Ang(1-7) mimic AVE 0991 is abolished in the aorta of mas-knockout mice. J Cardiovasc Pharmacol. 2005;46:274–279
  40. Masson R, Nicklin SA, Craig MA, McBride M, Gilday K, Gregorevic P, et al. Onset of experimental severe cardiac fibrosis is mediated by overexpression of angiotensin-converting enzyme 2. Hypertension. 2009;53:694–700
  41. Yamamoto K, Ohishi M, Katsuya T, Ito N, Ikushima M, Kaibe M, et al. Deletion of angiotensin-converting enzyme 2 accelerates pressure overload-induced cardiac dysfunction by increasing local angiotensin II. Hypertension. 2006;47:718–726
  42. Der Sarkissian S, Grobe JL, Yuan L, Narielwala DR, Walter GA, Katovich MJ, et al. Cardiac overexpression of angiotensin converting enzyme 2 protects the heart from ischemia-induced pathophysiology. Hypertension. 2008;51:712–718
  43. Huentelman MJ, Grobe JL, Vazquez J, Stewart JM, Mecca AP, Katovich MJ, et al. Protection from angiotensin II-induced cardiac hypertrophy and fibrosis by systemic lentiviral delivery of ACE2 in rats. Exp Physiol. 2005;90:783–790
  44. Burrell LM, Risvanis J, Kubota E, Dean RG, MacDonald PS, Lu S, et al. Myocardial infarction increases ACE2 expression in rat and humans. Eur Heart J. 2005;26:369–375
  45. Goulter AB, Goddard MJ, Allen JC, Clark KL. ACE2 gene expression is up-regulated in the human failing heart. BMC Med. 2004;2:19
  46. Epelman S, Tang WH, Chen SY, Van LF, Francis GS, Sen S. Detection of soluble angiotensin-converting enzyme 2 in heart failure: insights into the endogenous counter-regulatory pathway of the renin-angiotensin-aldosterone system. J Am Coll Cardiol. 2008;52:750–754
  47. Tallant EA, Gallagher PE. Angiotensin-(1-7) upregulates the mitogen-activated phosphatase DUSP1 in vascular smooth muscle cells. Hypertension. 2007;50:e77
  48. Tallant EA, Ferrario CM, Gallagher PE. Angiotensin-(1-7) inhibits growth of cardiac myocytes through activation of the mas receptor. Am J Physiol Heart Circ Physiol. 2005;289:H1560–H1566
  49. Loot AE, Roks AJ, Henning RH, Tio RA, Suurmeijer AJ, Boomsma F, et al. Angiotensin-(1-7) attenuates the development of heart failure after myocardial infarction in rats. Circulation. 2002;105:1548–1550

 Funded in part by National Institutes of Health grant 1RO1HL091191 to Dr. Greenberg.

 See page 784 for disclosure information.

PII: S1071-9164(10)00171-5

doi: 10.1016/j.cardfail.2010.04.002

Journal of Cardiac Failure
Volume 16, Issue 9 , Pages 777-785 , September 2010

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