Resveratrol induces mitochondrial biogenesis and ameliorates Ang II-induced cardiac remodeling in transgenic rats harboring human renin and angiotensinogen genes

Institute of Biomedicine, Pharmacology, University of Helsinki, Helsinki, Finland.
Blood pressure (Impact Factor: 1.81). 06/2010; 19(3):196-205. DOI: 10.3109/08037051.2010.481808
Source: PubMed


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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    • "Emerging evidence indicates that resveratrol increases mitochondrial biogenesis and reduces oxidative stress in a wide variety of age-associated disease models. It has been demonstrated that resveratrol induces mitochondrial biogenesis and ameliorates angiotensin II-induced cardiac remodeling through the activation of SIRT1, PGC-1α, and NRF [112]. Csiszar et al. [113] demonstrated that resveratrol induced activation of PGC-1α and NRF, increased mitochondrial mass and mitochondrial DNA content, and upregulated protein expression of the ETC constituents in endothelial cells. "
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    Oxidative Medicine and Cellular Longevity 04/2013; 2013(8):936436. DOI:10.1155/2013/936436 · 3.36 Impact Factor
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    • "Proteins in this system are thought as important regulators of blood pressure and are involved in the onset of hypertension [29-32]. Overexpression of REN leads to hypertension via chronic overproduction of AngII [33,34], and inhibiting the regulators of the RAS--such as REN--is a common treatment for hypertension [32]. Adiponectin (ADIPOQ) is an adipocytokine synthesized by the adipose tissue. "
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    BMC Genomics 12/2012; 13(8). DOI:10.1186/1471-2164-13-S8-S20 · 3.99 Impact Factor
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    • "Mitochondrial fusion and biogenesis have also been implicated in neuroprotective strategies against acute neural injury. Calpain inhibition provided neuroprotection against NMDA-induced neurotoxicity and was dependent on Opa-1, an enzyme critical for mitochondrial fusion (Jahani-Asl et al, 2011) Furthermore , induction of core elements of mitochondrial biogenesis have been observed using multiple preconditioning stimuli in neurons, such as sublethal hypoxia or hypoxia/ischemia (Gutsaeva et al, 2008), hyperbaric oxygen (Gutsaeva et al, 2006), and resveratrol (Dasgupta and Milbrandt, 2007; Biala et al, 2010). These stimuli have been well documented as neuroprotective strategies against acute brain injury, including cerebral ischemia and glutamate excitotoxicity. "
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