Document Detail

The nonpeptide AVE0991 attenuates myocardial hypertrophy as induced by angiotensin II through downregulation of transforming growth factor-beta1/Smad2 expression.
MedLine Citation:
PMID:  20676968     Owner:  NLM     Status:  MEDLINE    
The nonpeptide AVE0991 is expected to be a putative new drug for cardiovascular diseases. However, the mechanisms for the cardioprotective actions of AVE0991 are still not fully understood. We planned to determine whether AVE0991 attenuates the angiotensin II (AngII)-induced myocardial hypertrophy and whether these AVE0991 effects involved transforming growth factor beta1 (TGF-beta1) and Smad2. A rat model of neonatal myocardial hypertrophy was induced by AngII. The AngII group significantly increased in protein content, surface area, and [(3)H]leucine incorporation efficiency by cardiomyocytes, compared to those of the control group (P < 0.01). The AngII group also had elevated TGF-beta1 and Smad2 expression (P < 0.01). These AngII-induced changes were significantly attenuated by AVE0991 in a dose-dependent manner. In our study, these actions of AngII (10(-6) mol/l) were significantly inhibited by both concentrations of AVE0991 (10(-5) mol/l and 10(-7) mol/l). Moreover, the high AVE0991 group had significantly better inhibition of myocardial hypertrophy than the low AVE0991 group. Meanwhile, the beneficial effects of AVE0991 were completely abolished when the cardiomyocytes were pretreated with Ang-(1-7) receptor antagonist A-779 (10(-6) mol/l). These results suggested that AVE0991 prevented AngII-inducing myocardial hypertrophy in a dose-dependent fashion, a process that may be associated with the inhibition of TGF-beta1/Smad2 signaling.
Jian-Gui He; Sheng-Long Chen; Yi-Yi Huang; Yi-Li Chen; Yu-Gang Dong; Hong Ma
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't     Date:  2010-07-31
Journal Detail:
Title:  Heart and vessels     Volume:  25     ISSN:  1615-2573     ISO Abbreviation:  Heart Vessels     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-08-02     Completed Date:  2010-11-22     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  8511258     Medline TA:  Heart Vessels     Country:  Japan    
Other Details:
Languages:  eng     Pagination:  438-43     Citation Subset:  IM    
Department of Cardiology, First Affiliated Hospital of Sun Yat-sen University, Guangzhou, PR China.
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MeSH Terms
Angiotensin II / analogs & derivatives,  metabolism*,  pharmacology
Animals, Newborn
Cardiomegaly / metabolism,  pathology,  prevention & control*
Cardiovascular Agents / pharmacology*
Cell Size / drug effects
Cells, Cultured
Dose-Response Relationship, Drug
Imidazoles / pharmacology*
Myocytes, Cardiac / drug effects*,  metabolism,  pathology
Peptide Fragments / pharmacology
Proto-Oncogene Proteins / antagonists & inhibitors,  metabolism
RNA, Messenger / metabolism
Rats, Sprague-Dawley
Receptors, G-Protein-Coupled / antagonists & inhibitors,  metabolism
Signal Transduction / drug effects
Smad2 Protein / genetics,  metabolism*
Transforming Growth Factor beta1 / genetics,  metabolism*
Reg. No./Substance:
0/7-Ala-angiotensin (1-7); 0/AVE 0991; 0/Cardiovascular Agents; 0/Imidazoles; 0/Madh2 protein, rat; 0/Peptide Fragments; 0/Proto-Oncogene Proteins; 0/RNA, Messenger; 0/Receptors, G-Protein-Coupled; 0/Smad2 Protein; 0/Transforming Growth Factor beta1; 0/proto-oncogene proteins c-mas-1; 11128-99-7/Angiotensin II

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