© 1994 by European Society of Cardiology
Copyright © 1994, European Society of Cardiology
Cardiac angiotensin converting enzyme and myocardial fibrosis in the rat
University of Missouri Health Sciences Center, MA432 Medical Science Building, Columbia, MO 65212, USA—Division of Cardiology, Department of Internal Medicine: Y Sun, J P M Cleutjens, K T Weber; Department of Pathology: A A Diaz-Arias.
Correspondence to Dr Weber.
Objective: The aim was to test the hypothesis that cardiac angiotensin converting enzyme (ACE) is related to the accumulation of fibrous tissue in the heart. Methods: A model of tissue repair (pericardiotomy with left coronary artery ligation) was used, together with the following: quantitative in vitro autoradiography (125I-351A) to determine ACE binding density; immunohistochemistry (monoclonal ACE antibody, 9B9) to identify cells expressing ACE; and in situ hybridisation to localise cells expressing type I collagen mRNA. Age and sex matched rats receiving this operative procedure without subsequent infarction (sham operated) served as controls to those with left ventricular myocardial infarction. Serial heart sections obtained from each group at 3 days and at 1, 2, 4, and 8 weeks following operation were examined for morphological evidence of injury and inflammatory cells (haematoxylin/eosin) and fibrillar collagen (picrosirius red). Results: Following myocardial infarction: (a) on day 3, neutrophils and macrophages were present at the site of infarction, while fibrillar collagen and ACE binding were not increased compared with control; (b) at week 1, fibrillar collagen and ACE binding were present at the site of infarction and became progressively more advanced at 2, 4, and 8 weeks; (c) at week 2, there was increased ACE binding in the right ventricle and interventricular septum, when perivascular fibrosis of intramural coronary arteries and microscopic scars appeared, together with endomyocardial fibrosis of the septum; (d) there was marked ACE binding in the fibrosed visceral pericardium two weeks after operation in both myocardial infarction and sham operated groups; (e) there was type I collagen mRNA expression on postoperative week 1, localised within fibroblasts or fibroblast-like cells found at infarct and fibrous tissue sites in the right ventricle, septum, and pericardium; and (f) ACE-labelled cells included fibroblast-like cells, as well as macrophages and endothelial cells. Conclusions: Thus in this model of tissue repair, marked ACE binding density is associated with fibrillar collagen formation that appears within and remote to the site of myocardial infarction, including the pericardium. Cardiac ACE, originating from type I collagen producing cells, therefore represents an integral component of fibrous tissue formation in this rat model of tissue injury.
Cardiovascular Research 1994;28:1423-1432
KEYWORDS myocardial infarction; pericardial and myocardial fibrosis; autoradiography; monoclonal ACE antibody; fibrillar collagen; type I collagen; in situ hybridisation
This work was supported in part by NIH grant R01-HL-31701 and was conducted during Dr Cleutjens's tenure with the Netherlands Organization for Scientific Research (NWO) (Grant S93.221.92) and Netherlands Heart Foundation (Grant 90.282).
CiteULike 
Connotea 
Del.icio.us What's this?
This article has been cited by other articles:
|
|
 |
|
  Y. Sun Myocardial repair/remodelling following infarction: roles of local factors Cardiovasc Res, February 15, 2009; 81(3): 482 - 490. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 R. Mukherjee, J. T. Mingoia, J. A. Bruce, J. S. Austin, R. E. Stroud, G. P. Escobar, D. M. McClister Jr, C. M. Allen, M. A. Alfonso-Jaume, M. E. Fini, et al. Selective spatiotemporal induction of matrix metalloproteinase-2 and matrix metalloproteinase-9 transcription after myocardial infarction Am J Physiol Heart Circ Physiol, November 1, 2006; 291(5): H2216 - H2228. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. Wang, R. Ansari, Y. Sun, A. E. Postlethwaite, K. T. Weber, and M. F. Kiani The scar neovasculature after myocardial infarction in rats Am J Physiol Heart Circ Physiol, July 1, 2005; 289(1): H108 - H113. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. H. Freed, R. H. Cunnington, A. L. Dangerfield, J. S. Sutton, and I. M.C. Dixon Emerging evidence for the role of cardiotrophin-1 in cardiac repair in the infarcted heart Cardiovasc Res, March 1, 2005; 65(4): 782 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. C. Silva, C. E. Rochitte, J. S. Junior, J. Tsutsui, J. Andrade, E. E. Martinez, P. J. Moffa, J. C. Menegheti, R. Kalil-Filho, J. F. Ramires, et al. Late coronary artery recanalization effects on left ventricular remodelling and contractility by magnetic resonance imaging Eur. Heart J., January 1, 2005; 26(1): 36 - 43. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Pokharel, P. P. van Geel, U. C. Sharma, J. P.M. Cleutjens, H. Bohnemeier, X.-L. Tian, H. Schunkert, H. J.G.M. Crijns, M. Paul, and Y. M. Pinto Increased Myocardial Collagen Content in Transgenic Rats Overexpressing Cardiac Angiotensin-Converting Enzyme Is Related to Enhanced Breakdown of N-Acetyl-Ser-Asp-Lys-Pro and Increased Phosphorylation of Smad2/3 Circulation, November 9, 2004; 110(19): 3129 - 3135. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X.-L. Tian, Y. M. Pinto, O. Costerousse, W. M. Franz, A. Lippoldt, S. Hoffmann, T. Unger, and M. Paul Over-expression of angiotensin converting enzyme-1 augments cardiac hypertrophy in transgenic rats Hum. Mol. Genet., July 15, 2004; 13(14): 1441 - 1450. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. Tan, H. Wang, and F. H. H. Leenen Increases in brain and cardiac AT1 receptor and ACE densities after myocardial infarct in rats Am J Physiol Heart Circ Physiol, May 1, 2004; 286(5): H1665 - H1671. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. Westendorp, R. G Schoemaker, H. Buikema, D. de Zeeuw, D. J van Veldhuisen, and W. H van Gilst Dietary sodium restriction specifically potentiates left ventricular ACE inhibition by zofenopril, and is associated with attenuated hypertrophic response in rats with myocardial infarction Journal of Renin-Angiotensin-Aldosterone System, March 1, 2004; 5(1): 27 - 32. [Abstract] [PDF]
|
|
|
|
|
|
K. T Weber, Yao Sun, L. A Wodi, A. Munir, E. Jahangir, R. A Ahokas, I. C Gerling, A. E Postlethwaite, and K. J Warrington Toward a broader understanding of aldosterone in congestive heart failure Journal of Renin-Angiotensin-Aldosterone System, September 1, 2003; 4(3): 155 - 163. [Abstract] [PDF]
|
|
|
|
 |
|
 C.-M. Yu, K. W.-H. Lai, Y.-X. Chen, X.-R. Huang, and H. Y. Lan Expression of Macrophage Migration Inhibitory Factor in Acute Ischemic Myocardial Injury J. Histochem. Cytochem., May 1, 2003; 51(5): 625 - 631. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. Maki, Y. Nasa, K. Tanonaka, M. Takahashi, and S. Takeo Beneficial Effects of Sampatrilat, a Novel Vasopeptidase Inhibitor, on Cardiac Remodeling and Function of Rats with Chronic Heart Failure following Left Coronary Artery Ligation J. Pharmacol. Exp. Ther., April 1, 2003; 305(1): 97 - 105. [Abstract] [Full Text]
|
|
|
|
 |
|
 J. Peng, D. Gurantz, V. Tran, R. T. Cowling, and B. H. Greenberg Tumor Necrosis Factor-{alpha}-Induced AT1 Receptor Upregulation Enhances Angiotensin II-Mediated Cardiac Fibroblast Responses That Favor Fibrosis Circ. Res., December 13, 2002; 91(12): 1119 - 1126. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Chen, Y. Wei, G. C. Sharp, and H. Braley-Mullen Inhibition of TGF{beta}1 by Anti-TGF{beta}1 Antibody or Lisinopril Reduces Thyroid Fibrosis in Granulomatous Experimental Autoimmune Thyroiditis J. Immunol., December 1, 2002; 169(11): 6530 - 6538. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C.-M. Yu, G. L. Tipoe, K. Wing-Hon Lai, and C.-P. Lau Effects of combination of angiotensin-converting enzyme inhibitor and angiotensin receptor antagonist on inflammatory cellular infiltration and myocardial interstitial fibrosis after acute myocardial infarction J. Am. Coll. Cardiol., October 1, 2001; 38(4): 1207 - 1215. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. J Lijnen, V. V Petrov, and R. H Fagard Angiotensin II-induced stimulation of collagen secretion and production in cardiac fibroblasts is mediated via angiotensin II subtype 1 receptors Journal of Renin-Angiotensin-Aldosterone System, June 1, 2001; 2(2): 117 - 122. [Abstract] [PDF]
|
|
|
|
|
|
K. T Weber and Yao Sun Recruitable ACE and tissue repair in the infarcted heart Journal of Renin-Angiotensin-Aldosterone System, December 1, 2000; 1(4): 295 - 303. [PDF]
|
|
|
|
|
|
V. V Petrov, R. H Fagard, and P. J Lijnen Transforming growth factor-{beta}1 induces angiotensin-converting enzyme synthesis in rat cardiac fibroblasts during their differentiation to myofibroblasts Journal of Renin-Angiotensin-Aldosterone System, December 1, 2000; 1(4): 342 - 352. [Abstract] [PDF]
|
|
|
|
|
|
J. Hao, B. Wang, S. C. Jones, D. S. Jassal, and I. M. C. Dixon Interaction between angiotensin II and Smad proteins in fibroblasts in failing heart and in vitro Am J Physiol Heart Circ Physiol, December 1, 2000; 279(6): H3020 - H3030. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. V. Cohen, X.-M. Yang, T. Neumann, G. Heusch, and J. M. Downey Favorable Remodeling Enhances Recovery of Regional Myocardial Function in the Weeks After Infarction in Ischemically Preconditioned Hearts Circulation, August 1, 2000; 102(5): 579 - 583. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. G. St. J. Sutton and N. Sharpe Left Ventricular Remodeling After Myocardial Infarction : Pathophysiology and Therapy Circulation, June 27, 2000; 101(25): 2981 - 2988. [Full Text] [PDF]
|
|
|
|
 |
|
 W. C. De Mello and A. H. J. Danser Angiotensin II and the Heart : On the Intracrine Renin-Angiotensin System Hypertension, June 1, 2000; 35(6): 1183 - 1188. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Sun and K. T. Weber Infarct scar: a dynamic tissue Cardiovasc Res, May 1, 2000; 46(2): 250 - 256. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. Graf, M. Neuss, P. Stawowy, W. A. Hsueh, E. Fleck, and R. E. Law Angiotensin II and {alpha}v{beta}3 Integrin Expression in Rat Neonatal Cardiac Fibroblasts Hypertension, April 1, 2000; 35(4): 978 - 984. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. A. Walsh, J. Catravas, and J. Wharton Angiotensin converting enzyme in human synovium: increased stromal [125I]351A binding in rheumatoid arthritis Ann Rheum Dis, February 1, 2000; 59(2): 125 - 131. [Abstract] [Full Text]
|
|
|
|
|
|
A.H.J. Danser, J. J Saris, M. P Schuijt, and J. P van Kats Is there a local renin--angiotensin system in the heart? Cardiovasc Res, November 1, 1999; 44(2): 252 - 265. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C Wollert and H. Drexler The renin-angiotensin system and experimental heart failure Cardiovasc Res, September 1, 1999; 43(4): 838 - 849. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J.-S. Silvestre, C. Heymes, A. Oubenaissa, V. Robert, B. Aupetit-Faisant, A. Carayon, B. Swynghedauw, and C. Delcayre Activation of Cardiac Aldosterone Production in Rat Myocardial Infarction : Effect of Angiotensin II Receptor Blockade and Role in Cardiac Fibrosis Circulation, May 25, 1999; 99(20): 2694 - 2701. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Raut, J.-L. Rouleau, C. Blais Jr., H. Gosselin, G. Molinaro, M. G. Sirois, Y. Lepage, P. Crine, and A. Adam Bradykinin metabolism in the postinfarcted rat heart: role of ACE and neutral endopeptidase 24.11 Am J Physiol Heart Circ Physiol, May 1, 1999; 276(5): H1769 - H1779. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. E. Bishop and G. Lindahl Regulation of cardiovascular collagen synthesis by mechanical load Cardiovasc Res, April 1, 1999; 42(1): 27 - 44. [Full Text] [PDF]
|
|
|
|
|
|
S. Hafizi, J. Wharton, K. Morgan, S. P. Allen, A. H. Chester, J. D. Catravas, J. M. Polak, and M. H. Yacoub Expression of Functional Angiotensin-Converting Enzyme and AT1 Receptors in Cultured Human Cardiac Fibroblasts Circulation, December 8, 1998; 98(23): 2553 - 2559. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Katoh, K. Egashira, M. Usui, T. Ichiki, H. Tomita, H. Shimokawa, H. Rakugi, and A. Takeshita Cardiac Angiotensin II Receptors Are Upregulated by Long-Term Inhibition of Nitric Oxide Synthesis in Rats Circ. Res., October 5, 1998; 83(7): 743 - 751. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. P. van Kats, A. H. J. Danser, J. R. van Meegen, L. M. A. Sassen, P. D. Verdouw, and M. A. D. H. Schalekamp Angiotensin Production by the Heart : A Quantitative Study in Pigs With the Use of Radiolabeled Angiotensin Infusions Circulation, July 7, 1998; 98(1): 73 - 81. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. W. Brooks, O. H. L. Bing, K. G. Robinson, M. T. Slawsky, D. M. Chaletsky, and C. H. Conrad Effect of Angiotensin-Converting Enzyme Inhibition on Myocardial Fibrosis and Function in Hypertrophied and Failing Myocardium From the Spontaneously Hypertensive Rat Circulation, December 2, 1997; 96(11): 4002 - 4010. [Abstract] [Full Text]
|
|
|
|
|
|
K. T. Weber Extracellular Matrix Remodeling in Heart Failure : A Role for De Novo Angiotensin II Generation Circulation, December 2, 1997; 96(11): 4065 - 4082. [Full Text]
|
|
|
|
|
|
J. Fareh, R. M. Touyz, E. L. Schiffrin, and G. Thibault Cardiac Type-1 Angiotensin II Receptor Status in Deoxycorticosterone Acetate–Salt Hypertension in Rats Hypertension, November 1, 1997; 30(5): 1253 - 1259. [Abstract] [Full Text]
|
|
|
|
|
|
H. Ju, S. Zhao, D. S Jassal, and I. M.C Dixon Effect of AT1 receptor blockade on cardiac collagen remodeling after myocardial infarction Cardiovasc Res, August 1, 1997; 35(2): 223 - 232. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. H. J. Danser, C. A. M. van Kesteren, W. A. Bax, M. Tavenier, F. H. M. Derkx, P. R. Saxena, and M. A. D. H. Schalekamp Prorenin, Renin, Angiotensinogen, and Angiotensin-Converting Enzyme in Normal and Failing Human Hearts : Evidence for Renin Binding Circulation, July 1, 1997; 96(1): 220 - 226. [Abstract] [Full Text]
|
|
|
|
|
|
Y. Sun, F. J.A Ramires, and K. T Weber Fibrosis of atria and great vessels in response to angiotensin II or aldosterone infusion Cardiovasc Res, July 1, 1997; 35(1): 138 - 147. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. C. Wollert, R. Studer, K. Doerfer, E. Schieffer, C. Holubarsch, H. Just, and H. Drexler Differential Effects of Kinins on Cardiomyocyte Hypertrophy and Interstitial Collagen Matrix in the Surviving Myocardium After Myocardial Infarction in the Rat Circulation, April 1, 1997; 95(7): 1910 - 1917. [Abstract] [Full Text]
|
|
|
|
|
|
S. Hokimoto, H. Yasue, K. Fujimoto, H. Yamamoto, K. Nakao, K. Kaikita, R. Sakata, and E. Miyamoto Expression of Angiotensin-Converting Enzyme in Remaining Viable Myocytes of Human Ventricles After Myocardial Infarction Circulation, October 1, 1996; 94(7): 1513 - 1518. [Abstract] [Full Text]
|
|
|
|
|
|
F. Pieruzzi, Z. A. Abassi, and H. R. Keiser Expression of Renin-Angiotensin System Components in the Heart, Kidneys, and Lungs of Rats With Experimental Heart Failure Circulation, November 15, 1995; 92(10): 3105 - 3112. [Abstract] [Full Text]
|
|
|
|
|
|
N. Iwai, H. Shimoike, and M. Kinoshita Cardiac Renin-Angiotensin System in the Hypertrophied Heart Circulation, November 1, 1995; 92(9): 2690 - 2696. [Abstract] [Full Text]
|
|