Document Detail


Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes.
MedLine Citation:
PMID:  20429690     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
There is compelling evidence to indicate an important role for increased local renin-angiotensin system activity in the pathogenesis of cardiac hypertrophy and heart failure. Resveratrol is a natural polyphenol that activates SIRT1, a novel cardioprotective and longevity factor having NAD(+)-dependent histone deacetylase activity. We tested the hypothesis whether resveratrol could prevent from angiotensin II (Ang II)-induced cardiovascular damage. Four-week-old double transgenic rats harboring human renin and human angiotensinogen genes (dTGR) were treated for 4 weeks either with SIRT1 activator resveratrol or SIRT1 inhibitor nicotinamide. Untreated dTGR and their normotensive Sprague-Dawley control rats (SD) received vehicle. Untreated dTGR developed severe hypertension as well as cardiac hypertrophy, and showed pronounced cardiovascular mortality compared with normotensive SD rats. Resveratrol slightly but significantly decreased blood pressure, ameliorated cardiac hypertrophy and prevented completely Ang II-induced mortality, whereas nicotinamide increased blood pressure without significantly influencing cardiac hypertrophy or survival. Resveratrol decreased cardiac ANP mRNA expression and induced cardiac mRNA expressions of mitochondrial biogenesis markers peroxisome proliferator-activated receptor-gamma coactivator (PGC-1alpha), mitochondrial transcription factor (Tfam), nuclear respiratory factor 1 (NRF-1) and cytochrome c oxidase subunit 4 (cox4). Resveratrol dose-dependently increased SIRT1 activity in vitro. Our findings suggest that the beneficial effects of SIRT1 activator resveratrol on Ang II-induced cardiac remodeling are mediated by blood pressure-dependent pathways and are linked to increased mitochondrial biogenesis.
Authors:
Agnieszka Biala; Eveliina Tauriainen; Antti Siltanen; Jin Shi; Saara Merasto; Marjut Louhelainen; Essi Martonen; Piet Finckenberg; Dominik N Muller; Eero Mervaala
Publication Detail:
Type:  Comparative Study; Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Blood pressure     Volume:  19     ISSN:  1651-1999     ISO Abbreviation:  Blood Press.     Publication Date:  2010 Jun 
Date Detail:
Created Date:  2010-05-20     Completed Date:  2010-08-20     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9301454     Medline TA:  Blood Press     Country:  England    
Other Details:
Languages:  eng     Pagination:  196-205     Citation Subset:  IM    
Affiliation:
Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
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MeSH Terms
Descriptor/Qualifier:
Angiotensin II / genetics,  metabolism,  pharmacology*
Angiotensinogen / genetics*,  metabolism,  pharmacology
Animals
Blood Pressure / drug effects,  genetics
Cardiomegaly / genetics,  metabolism,  physiopathology
Genes / drug effects
Heart / physiopathology
Humans
Hypertension / genetics,  metabolism,  pathology
Male
Mitochondria / genetics,  metabolism,  pathology
Rats
Rats, Sprague-Dawley
Rats, Transgenic
Renin / blood,  genetics*,  metabolism
Renin-Angiotensin System / drug effects,  genetics
Stilbenes
Chemical
Reg. No./Substance:
0/Stilbenes; 11002-13-4/Angiotensinogen; 11128-99-7/Angiotensin II; 501-36-0/resveratrol; EC 3.4.23.15/Renin

From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine


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