The aims of this study were to compare human cardiac angiotensin-II-forming activity (AIIFA) between the intact area of control autopsy hearts without cardiac disease (n = 10) and the infarcted or non-infarcted area of autopsy hearts with myocardial infarction (MI, n = 7) and to determine responsible angiotensin-II-forming enzymes. Cardiac total and chymase-dependent AIIFAs were significantly higher in the infarcted and non-infarcted myocardium than those in non-MI heart, while angiotensin-converting enzyme-dependent AIIFA increased only in the infarcted myocardium. The density of chymase antibody-positive mast cells in the non-infarcted area of MI heart correlated positively with total or chymase-dependent AIIFA. Augmented AIIFA was also detected in the left atrium of post-MI hearts. Our results indicated that cardiac angiotensin II formation could be activated in the infarcted as well as in non-infarcted myocardium of the post-MI human heart.

Keywords:
Angiotensin-II-forming enzyme, Chymase, Angiotensin-converting enzyme, Mast cell, Inflammatory cell, Cardiac renin-angiotensin system, Myocardial infarction, Cardiac remodeling
1.
Hokimoto S, Yasue H, Fujimoto K, Yamamoto H, Nakao K, Kaikita K, Sakata R, Miyamoto E: Expression of angiotensin-converting enzyme in remaining viable myocytes of human ventricles after myocardial infarction. Circulation 1996;94:1513–1518.
2.
Johnston CI, Mooser V, Sun Y, Fabris B: Changes in cardiac angiotensin converting enzyme after myocardial infarction and hypertrophy in rats. Clin Exp Pharmacol 1991;18:107–110.
3.
Ertl G, Kloner RA, Alexander RW, Braunwald E: Limitation of experimental infarct size by an angiotensin-converting enzyme inhibitor. Circulation 1982;65:40–48.
4.
Schunkert H, Jackson B, Tang SS, Schoen FJ, Smits JFM, Apstein CS, Lorell BH: Distribution and functional significance of cardiac angiotensin converting enzyme in hypertrophied rat hearts. Circulation 1993;87:1328–1339.
5.
Schorb W, Booz GW, Dostal DE, Conrad KM, Chang KC, Baker KM: Angiotensin II is mitogenic in neonatal rat cardiac fibroblasts. Circ Res 1993;72:1245–1254.
6.
Villarreal FJ, Kim NN, Ungab GD, Printz MP, Dillmann WH: Identification of functional angiotensin II receptors on rat cardiac fibroblasts. Circulation 1993;88:2849–2861.
7.
Pfeffer MA, Braunwald E, Moye LA, Basta L, Brown EJ Jr, Cuddy TE, Davis BR, Geltman EM, Goldman S, Flaker GC, Klein M, Lamas GA, Packer M, Rouleau J, Rouleau JL, Rutherford J, Wertheimer JH, Hawkins CM, on behalf of the SAVE Investigators: Effect of captopril on mortality and morbidity in patients with left ventricular dysfunction after myocardial infarction. Results of the survival and ventricular enlargement trial. N Engl J Med 1992;327:669–677.
8.
Pitt B, Segal R, Martinez FA, Meurers G, Cowley AJ, Thomas I, Deedwania PC, Ney DE, Snavely DB, Chang PI: Randomised trial of losartan versus captopril in patients over 65 with heart failure. Lancet 1997;349:747–752.
9.
Pitt B, Poole-Wilson PA, Segal R, Martinez FA, Dickstein K, Camm AJ, Konstam MA, Riegger G, Klinger GH, Neaton J, Sharma D, Thiyagarajan B: Effect of losartan compared with captopril on mortality in patients with symptomatic heart failure: Randomised trial. The Losartan Heart Failure Survival Study ELITE II. Lancet 2000;355:1582–1587.
10.
Arakawa K: Serine protease angiotensin II systems. J Hypertens 1996;14(suppl):S3–S7.
11.
Noda K, Sasaguri M, Ideishi M, Ikeda M, Arakawa K: Role of locally formed angiotensin II and bradykinin in the reduction of myocardial infarct size in dogs. Cardiovasc Res 1993;27:334–340.
12.
Miura S, Ideishi M, Sakai T, Motoyama M, Kinoshita A, Sasaguri M, Tanaka H, Shindo M, Arakawa K: Angiotensin II formation by an alternative pathway during exercise in humans. J Hypertens 1994;12:1177–1181.
13.
Urata H, Kinoshita A, Misono KS, Bumpus FM, Husain A: Identification of a highly specific chymase as the major angiotensin II-forming enzyme in the human heart. J Biol Chem 1990;265:22348–22357.
14.
Urata H, Boehm KD, Philip A, Kinoshita A, Gabrovsek J, Bumpus FM, Husain A: Cellular localization and regional distribution of an angiotensin II-forming chymase in the heart. J Clin Invest 1993;91:1269–1281.
15.
Urata H, Strobel F, Ganten D: Widespread tissue distribution of human chymase. J Hypertens 1994;12(suppl):S17–S22.
16.
Ihara M, Urata H, Kinoshita A, Suzumiya J, Sasaguri M, Kikuchi M, Ideishi M, Arakawa K: Increased chymase-dependent angiotensin II formation in human atherosclerotic aorta. Hypertension 1999;33:1399–1405.
17.
Akasu M, Urata H, Kinoshita A, Sasaguri M, Ideishi M, Arakawa K: Differences in tissue angiotensin II-forming pathways by species and organs in vitro. Hypertension 1998;32:514–520.
18.
Hirsch AT, Talsness CE, Schunkert H, Paul M, Dzau VJ: Tissue-specific activation of cardiac angiotensin converting enzyme in experimental heart failure. Circ Res 1991;69:475–482.
19.
Litwin SE, Katz SE, Morgan JP, Douglas PS: Serial echocardiographic assessment of left ventricular geometry and function after large myocardial infarction in the rat. Circulation 1994;89:345–354.
20.
Shiota N, Jin D, Takai S, Kawamura T, Koyama M, Nakamura N, Miyazaki M: Chymase is activated in the hamster heart following ventricular fibrosis during the chronic stage of hypertension. FEBS Lett 1997;406:301–304.
21.
Nakayama S, Uehara Y, Urata H, Kinoshita A, Noda K, Sasaguri M, Ideishi M, Suzumiya J, Kikuchi M, Arakawa K: Differential regulation of angiotensin II-forming enzymes by tissues in 2-kidney 1 clip hypertensive hamster. J Hypertens 1998;16(suppl 2):S124.
22.
Dell’Italia LJ, Meng QC, Balcells E, Straeter Knowlen IM, Hankes GH, Dillon R, Cartee RE, Orr R, Bishop SP, Oparil S, Elton TS: Increased ACE and chymase-like activity in cardiac tissue of dogs with chronic mitral regurgitation. Am J Physiol 1995;269:H2065–H2073.
23.
Nakashima H, Kumagai K, Urata H, Gondo N, Ideishi M, Arakawa K: Angiotensin II antagonist prevents electrical remodeling in atrial fibrillation. Circulation 2000;101:2612–2617.
24.
Urata H, Healy B, Stewart RW, Bumpus FM, Husain A: Angiotensin II receptors in normal and failing human hearts. J Clin Endocrinol Metab 1989;69:54–66.
25.
Engels W, Reiters PH, Daemen MJ, Smits JF, Van der Vusse GJ: Transmural changes in mast cell density in rat heart after infarct induction in vivo. J Pathol 1995;177:423–429.
© 2001 S. Karger AG, Basel
2001
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