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Impairment of Cardiac Function and Remodeling Induced by Myocardial Infarction in Rats are Attenuated by the Nonpeptide Angiotensin-(1-7) Analog AVE 0991.

Authors: Zeng, WT  Chen, WY  Leng, XY  Tang, LL  Sun, XT  Li, CL  Dai, G 
Citation: Zeng WT, etal., Cardiovasc Ther. 2010 Dec 19. doi: 10.1111/j.1755-5922.2010.00255.x.
Pubmed: (View Article at PubMed) PMID:21167013
DOI: Full-text: DOI:10.1111/j.1755-5922.2010.00255.x

Aims: We evaluated effects of the nonpeptide angiotensin (ANG)-(1-7) analog AVE 0991 (AVE) on cardiac function and remodeling as well as transforming growth factor-beta1 (TGF-beta1)/tumor necrosis factor-alpha (TNF-alpha) expression in myocardial infarction rat models. Methods and Results: Sprague-Dawley rats underwent either sham surgery or coronary ligation. They were divided into four groups: sham, control, AVE, and AVE+A-779 [[D-Ala(7) ]-ANG-(1-7), a selective antagonist for the ANG-(1-7)] group. After 4 weeks of treatment, the AVE group displayed a significant elevation in left ventricular fractional shorting (LVFS) (25.5 +/- 7.3% vs. 18.4 +/- 3.3%, P < 0.05) and left ventricular ejection fraction (LVEF) (44.8 +/- 7.6% vs. 32.7 +/- 6.5%, P < 0.05) when compared to the control group, but no effects on the left ventricular end-diastolic and end-systolic diameters (LVDd and LVDs, respectively) were observed. In addition, we found that the myocyte diameter (18 +/- 2 mum vs. 22 +/- 4 mum, P < 0.05), infarct size (42.6 +/- 3.6% vs. 50.9 +/- 4.4%, P < 0.001) and collagen volume fraction (CVF) (16.4 +/- 2.2% vs. 25.3 +/- 3.2%, P < 0.001) were significantly reduced in the AVE group when compared to the control group. There were no differences in LVFS, LVEF, myocyte diameter, and infarct size between the control and AVE+A-779 groups. AVE also markedly attenuated the increased mRNA expression of collagen I (P < 0.001) and collagen III (P < 0.001) and inhibited the overexpression of TGF-beta1 (P < 0.05) and TNF-alpha (P < 0.05) compared to the control group. Conclusion: AVE could improve cardiac function and attenuate ventricular remodeling in MI rat models. It may involve the inhibition of inflammatory factors TGF-beta1/TNF-alpha overexpression and the action on the specific receptor Mas of ANG-(1-7).

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CRRD Object Information
CRRD ID: 5129191
Created: 2011-03-28
Species: All species
Last Modified: 2011-03-28
Status: ACTIVE



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RGD is funded by grant HL64541 from the National Heart, Lung, and Blood Institute on behalf of the NIH.