| Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes. | |
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MedLine Citation:
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PMID: 20429690 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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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. |
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Authors:
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Agnieszka Biala; Eveliina Tauriainen; Antti Siltanen; Jin Shi; Saara Merasto; Marjut Louhelainen; Essi Martonen; Piet Finckenberg; Dominik N Muller; Eero Mervaala |
Publication Detail:
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Type: Comparative Study; Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Blood pressure Volume: 19 ISSN: 1651-1999 ISO Abbreviation: Blood Press. Publication Date: 2010 Jun |
Date Detail:
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Created Date: 2010-05-20 Completed Date: 2010-08-20 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 9301454 Medline TA: Blood Press Country: England |
Other Details:
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Languages: eng Pagination: 196-205 Citation Subset: IM |
Affiliation:
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Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland. |
Export Citation:
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APA/MLA Format Download EndNote Download BibTex |
| MeSH Terms | |
Descriptor/Qualifier:
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Angiotensin II
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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:
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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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