This Article Full Text Full Text (PDF) Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Request Permissions Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Perry, G. J. Articles by Dell’Italia, L. J. Search for Related Content PubMed PubMed Citation Articles by Perry, G. J. Articles by Dell’Italia, L. J. Pubmed/NCBI databases Compound via MeSH Substance via MeSH Medline Plus Health Information Arteriovenous Malformations Related Collections Remodeling ACE/Angiotension receptors Genetically altered mice Hypertrophy Echocardiography

(Circulation. 2001;103:1012.)
© 2001 American Heart Association, Inc.

Basic Science Reports

Genetic Variation in Angiotensin-Converting Enzyme Does Not Prevent Development of Cardiac Hypertrophy or Upregulation of Angiotensin II in Response to Aortocaval Fistula

Presented at the 48th Annual Scientific Sessions, New Orleans, La, March 7–10, 1999, and published in abstract form (J Am Coll Cardiol. 1999;33:171A).

Gilbert J. Perry, MD; Tatsuhiko Mori, MD, PhD; Chih-Chang Wei, PhD; Xiao Yan Xu, MD; Yiu-Fai Chen, PhD; Suzanne Oparil, MD; Pamela Lucchesi, PhD; Louis J. Dell’Italia, MD

From the Birmingham VA Medical Center (G.J.P., L.J.D.) and the University of Alabama at Birmingham (G.J.P., T.M., C.-C.W., X.Y.X., Y.-F.C., S.O., P.L., L.J.D.).

Correspondence to Gilbert J. Perry, MD, 700 S 19th St (111H), Birmingham, AL 35233. E-mail gilbert.perry{at}med.va.gov

Background—Experimental and clinical evidence suggests that angiotensin II may be an important mediator of cardiac hypertrophy in response to hemodynamic stress. We investigated the effect of genetic variation in angiotensin-converting enzyme (ACE) on the development of cardiac hypertrophy and left ventricular (LV) dysfunction in response to volume overload.

Methods and Results—Male heterozygous ACE knockout (1/0) and wild-type (1/1) mice were studied 4 weeks after the creation of an aortocaval fistula (ACF). The LV weight/body weight ratio increased 74% in ACF versus sham-operated control mice but did not differ between genotypes. Echocardiographic circumferential stress versus rate-corrected velocity of circumferential shortening curves demonstrated depressed LV function in ACF versus sham-operated mice but no difference between genotypes. LV ACE activity was higher in 1/1 versus 1/0 mice and in ACF versus sham-operated mice, and it increased significantly more in the 1/1 versus the 1/0 mice after ACF (P<0.001 for effect of genotype, ACF/sham operation, and interaction term). LV angiotensin II was higher in ACF versus sham-operated mice but did not differ between genotypes, despite 3-fold higher LV ACE activity in ACF 1/1 versus ACF 1/0 mice.

Conclusions—ACE underexpression does not prevent cardiac hypertrophy or LV dysfunction in response to volume overload. LV angiotensin II is unaffected by ACE genotype, both at baseline and after volume overload, indicating that the heart can maintain angiotensin II levels across a broad range of genetic ACE variation under both physiological and pathophysiological conditions.

Key Words: hypertrophy • angiotensin • fistula • genes

This article has been cited by other articles:

				G. L. Brower, S. P. Levick, and J. S. Janicki Inhibition of matrix metalloproteinase activity by ACE inhibitors prevents left ventricular remodeling in a rat model of heart failure Am J Physiol Heart Circ Physiol, June 1, 2007; 292(6): H3057 - H3064. [Abstract] [Full Text] [PDF]

				T. Nishikimi, J. R. Hagaman, N. Takahashi, H.-S. Kim, H. Matsuoka, O. Smithies, and N. Maeda Increased susceptibility to heart failure in response to volume overload in mice lacking natriuretic peptide receptor-A gene Cardiovasc Res, April 1, 2005; 66(1): 94 - 103. [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]

				V. Franco, Y.-F. Chen, S. Oparil, J. A. Feng, D. Wang, F. Hage, and G. Perry Atrial Natriuretic Peptide Dose-Dependently Inhibits Pressure Overload-Induced Cardiac Remodeling Hypertension, November 1, 2004; 44(5): 746 - 750. [Abstract] [Full Text] [PDF]

				T. Mori, Y.-F. Chen, J. A. Feng, T. Hayashi, S. Oparil, and G. J Perry Volume overload results in exaggerated cardiac hypertrophy in the atrial natriuretic peptide knockout mouse Cardiovasc Res, March 1, 2004; 61(4): 771 - 779. [Abstract] [Full Text] [PDF]

				C.-C. Wei, P. A. Lucchesi, J. Tallaj, W. E. Bradley, P. C. Powell, and L. J. Dell'Italia Cardiac interstitial bradykinin and mast cells modulate pattern of LV remodeling in volume overload in rats Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H784 - H792. [Abstract] [Full Text] [PDF]

				W. M Aartsen, M. P Schuijt, A.H.J. Danser, M. J.A.P Daemen, and J. F.M Smits The role of locally expressed angiotensin converting enzyme in cardiac remodeling after myocardial infarction in mice Cardiovasc Res, November 1, 2002; 56(2): 205 - 213. [Abstract] [Full Text] [PDF]

				C.-C. Wei, B. Tian, G. Perry, Q. C. Meng, Y.-F. Chen, S. Oparil, and L. J. Dell'Italia Differential ANG II generation in plasma and tissue of mice with decreased expression of the ACE gene Am J Physiol Heart Circ Physiol, June 1, 2002; 282(6): H2254 - H2258. [Abstract] [Full Text] [PDF]