(Circulation. 1995;92:1387-1388.)
© 1995 American Heart Association, Inc.
Articles |
Angiotensin-Converting Enzyme in the Human Heart
Effect of the Deletion/Insertion Polymorphism
From the Cardiovasculair Onderzoeksinstituut Erasmus Universiteit Rotterdam (COEUR), Erasmus University, Rotterdam, Netherlands (A.H.J.D., M.A.D.H.S., W.A.B., A.M.vdB., P.R.S.), and the Medizinische Klinik II, University of Regensburg, Germany (G.A.J.R., H.S.).
Correspondence to A.H. Jan Danser, PhD, COEUR/Department of Pharmacology, Room EE1418b, Erasmus University, Dr Molewaterplein 50, 3015 GE Rotterdam, Netherlands.
Background An insertion (I)/deletion (D) polymorphism of the angiotensin-converting enzyme (ACE) gene has been associated with differences in the plasma levels of ACE as well as with myocardial infarction, cardiomyopathy, left ventricular hypertrophy, and coronary artery disease.
Methods and Results We determined the cardiac ACE activity and the ACE genotype in 71 subjects who died of noncardiac disorders. Cardiac ACE activity was significantly higher (P<.01) in subjects with the ACE DD genotype (12.7±1.9 mU/g wet wt) compared with subjects with the ID (8.7±0.8 mU/g) and the II (9.1±1.0 mU/g) genotypes. This difference was independent of sex, age, and the time required for tissue collection.
Conclusions Cardiac ACE activity is highest in subjects with the DD genotype. Elevated cardiac ACE activity in these subjects may result in increased cardiac angiotensin II levels, and this may be a mechanism underlying the reported association between the ACE deletion polymorphism and the increased risk for several cardiovascular disorders.
Key Words: genetics • angiotensin
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P. P. van Geel, Y. M. Pinto, A. A. Voors, H. Buikema, M. Oosterga, H. J. G. M. Crijns, and W. H. van Gilst Angiotensin II Type 1 Receptor A1166C Gene Polymorphism Is Associated With an Increased Response to Angiotensin II in Human Arteries Hypertension, March 1, 2000; 35(3): 717 - 721. [Abstract] [Full Text] [PDF]
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A. J. Marian, F. Safavi, L. Ferlic, J. K. Dunn, A. M. Gotto, and C. M. Ballantyne Interactions between angiotensin-I converting enzyme insertion/deletion polymorphism and response of plasma lipids and coronary atherosclerosis to treatment with fluvastatin: The lipoprotein and coronary atherosclerosis study J. Am. Coll. Cardiol., January 1, 2000; 35(1): 89 - 95. [Abstract] [Full Text] [PDF]
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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]
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S. Myerson, H. Hemingway, R. Budget, J. Martin, S. Humphries, and H. Montgomery Human angiotensin I-converting enzyme gene and endurance performance J Appl Physiol, October 1, 1999; 87(4): 1313 - 1316. [Abstract] [Full Text] [PDF]
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B. T. Heijmans, R. G. J. Westendorp, D. L. Knook, C. Kluft, and P. E. Slagboom Angiotensin I-converting enzyme and plasminogen activator inhibitor-1 gene variants: risk of mortality and fatal cardiovascular disease in an elderly population-based cohort J. Am. Coll. Cardiol., October 1, 1999; 34(4): 1176 - 1183. [Abstract] [Full Text] [PDF]
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K. F. Hilgers, M. R. W. Langenfeld, M. Schlaich, R. Veelken, and R. E. Schmieder 1166 A/C Polymorphism of the Angiotensin II Type 1 Receptor Gene and the Response to Short-Term Infusion of Angiotensin II Circulation, September 28, 1999; 100(13): 1394 - 1399. [Abstract] [Full Text] [PDF]
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D. Henrion, J. Benessiano, I. Philip, S. Vuillaumier-Barrot, M. Iglarz, G. Plantefeve, D. Chatel, U. Hvass, G. Durand, J.-M. Desmonts, et al. The deletion genotype of the angiotensin I-converting enzyme is associated with an increased vascular reactivity in vivo and in vitro J. Am. Coll. Cardiol., September 1, 1999; 34(3): 830 - 836. [Abstract] [Full Text] [PDF]
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R. R. Taylor, C. D. S. Mamotte, K. Fallon, and F. M. van Bockxmeer Elite athletes and the gene for angiotensin-converting enzyme J Appl Physiol, September 1, 1999; 87(3): 1035 - 1037. [Abstract] [Full Text] [PDF]
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J. Hung, B. M. McQuillan, M. Nidorf, P. L. Thompson, and J. P. Beilby Angiotensin-Converting Enzyme Gene Polymorphism and Carotid Wall Thickening in a Community Population Arterioscler. Thromb. Vasc. Biol., August 1, 1999; 19(8): 1969 - 1974. [Abstract] [Full Text] [PDF]
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A. Prasad, S. Husain, and A. A. Quyyumi Abnormal flow-mediated epicardial vasomotion in human coronary arteries is improved by angiotensin-converting enzyme inhibition: A potential role of bradykinin J. Am. Coll. Cardiol., March 1, 1999; 33(3): 796 - 804. [Abstract] [Full Text] [PDF]
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S. Ueda, P. A. Meredith, J. J. Morton, J. M. C. Connell, and H. L. Elliott ACE (I/D) Genotype as a Predictor of the Magnitude and Duration of the Response to an ACE Inhibitor Drug (Enalaprilat) in Humans Circulation, November 17, 1998; 98(20): 2148 - 2153. [Abstract] [Full Text] [PDF]
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A. P. R. M. Osterop, M. J. M. Kofflard, L. A. Sandkuijl, F. J. t. Cate, R. Krams, M. A. D. H. Schalekamp, and A. H. J. Danser AT1 Receptor A/C1166 Polymorphism Contributes to Cardiac Hypertrophy in Subjects With Hypertrophic Cardiomyopathy Hypertension, November 1, 1998; 32(5): 825 - 830. [Abstract] [Full Text] [PDF]
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 E. Villard, A. Alonso, M. Agrapart, M. Challah, and F. Soubrier Induction of Angiotensin I-converting Enzyme Transcription by a Protein Kinase C-dependent Mechanism in Human Endothelial Cells J. Biol. Chem., September 25, 1998; 273(39): 25191 - 25197. [Abstract] [Full Text] [PDF]
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M. Challah, E. Villard, M. Philippe, A. Ribadeau-Dumas, B. Giraudeau, P. Janiak, J.-P. Vilaine, F. Soubrier, and J.-B. Michel Angiotensin I-Converting Enzyme Genotype Influences Arterial Response to Injury in Normotensive Rats Arterioscler. Thromb. Vasc. Biol., February 1, 1998; 18(2): 235 - 243. [Abstract] [Full Text] [PDF]
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D.-K. Kim, J.-W. Kim, S. Kim, H.-C. Gwon, J.-C. Ryu, J.-E. Huh, J.-A Choo, Y. Choi, C.-H. Rhee, and W.-R. Lee Polymorphism of Angiotensin Converting Enzyme Gene Is Associated With Circulating Levels of Plasminogen Activator Inhibitor-1 Arterioscler. Thromb. Vasc. Biol., November 1, 1997; 17(11): 3242 - 3247. [Abstract] [Full Text]
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M. Margaglione, E. Grandone, G. Vecchione, G. Cappucci, N. Giuliani, D. Colaizzo, E. Celentano, S. Panico, and G. Di Minno Plasminogen Activator Inhibitor-1 (PAI-1) Antigen Plasma Levels in Subjects Attending a Metabolic Ward: Relation to Polymorphisms of PAI-1 and Angiontensin Converting Enzyme (ACE) Genes Arterioscler. Thromb. Vasc. Biol., October 1, 1997; 17(10): 2082 - 2087. [Abstract] [Full Text]
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Y. Watanabe, T. Ishigami, Y. Kawano, T. Umahara, A. Nakamori, S. Mizushima, K. Hibi, I. Kobayashi, K. Tamura, H. Ochiai, et al. Angiotensin-Converting Enzyme Gene I/D Polymorphism and Carotid Plaques in Japanese Hypertension, September 1, 1997; 30(3): 569 - 573. [Abstract] [Full Text]
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K. Hibi, T. Ishigami, K. Kimura, M. Nakao, T. Iwamoto, K. Tamura, T. Nemoto, T. Shimizu, Y. Mochida, H. Ochiai, et al. Angiotensin-Converting Enzyme Gene Polymorphism Adds Risk for the Severity of Coronary Atherosclerosis in Smokers Hypertension, September 1, 1997; 30(3): 574 - 579. [Abstract] [Full Text]
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D. N. Muller, J. Bohlender, K. F. Hilgers, D. Dragun, O. Costerousse, J. Menard, and F. C. Luft Vascular Angiotensin-Converting Enzyme Expression Regulates Local Angiotensin II Hypertension, January 1, 1997; 29(1): 98 - 104. [Abstract] [Full Text]
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A. Busjahn, H. Knoblauch, M. Knoblauch, J. Bohlender, M. Menz, H.-D. Faulhaber, A. Becker, H. Schuster, and F. C. Luft Angiotensin-Converting Enzyme and Angiotensinogen Gene Polymorphisms, Plasma Levels, Cardiac Dimensions A Twin Study: A Twin Study Hypertension, January 1, 1997; 29(1): 165 - 170. [Abstract] [Full Text] [PDF]
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K. J. McLaughlin, P. N. Harden, S. Ueda, J. M. Boulton-Jones, J. M.C. Connell, and A. G. Jardine The Role of Genetic Polymorphisms of Angiotensin-Converting Enzyme in the Progression of Renal Diseases Hypertension, November 1, 1996; 28(5): 912 - 915. [Abstract] [Full Text]
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A. Benetos, S. Gautier, S. Ricard, J. Topouchian, R. Asmar, O. Poirier, E. Larosa, L. Guize, M. Safar, F. Soubrier, et al. Influence of Angiotensin-Converting Enzyme and Angiotensin II Type 1 Receptor Gene Polymorphisms on Aortic Stiffness in Normotensive and Hypertensive Patients Circulation, August 15, 1996; 94(4): 698 - 703. [Abstract] [Full Text]
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M. Hosoi, Y. Nishizawa, K. Kogawa, T. Kawagishi, T. Konishi, K. Maekawa, M. Emoto, S. Fukumoto, A. Shioi, T. Shoji, et al. Angiotensin-Converting Enzyme Gene Polymorphism Is Associated With Carotid Arterial Wall Thickness in Non–Insulin-Dependent Diabetic Patients Circulation, August 15, 1996; 94(4): 704 - 707. [Abstract] [Full Text]
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D. R.J. Singer, C. G. Missouris, and S. Jeffery Angiotensin-Converting Enzyme Gene Polymorphism: What to Do About All the Confusion? Circulation, August 1, 1996; 94(3): 236 - 239. [Full Text]
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M. Eyries, A. Michaud, J. Deinum, M. Agrapart, J. Chomilier, C. Kramers, and F. Soubrier Increased Shedding of Angiotensin-converting Enzyme by a Mutation Identified in the Stalk Region J. Biol. Chem., February 16, 2001; 276(8): 5525 - 5532. [Abstract] [Full Text] [PDF]
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