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PGC-1{alpha} Attenuates Neointimal Formation via Inhibition of Vascular Smooth Muscle Cell Migration in the Injured Rat Carotid Artery.

Authors: Qu, A  Jiang, C  Xu, M  Zhang, Y  Zhu, Y  Xu, Q  Zhang, C  Wang, X 
Citation: Qu A, etal., Am J Physiol Cell Physiol. 2009 Jun 24.
Pubmed: (View Article at PubMed) PMID:19553562
DOI: Full-text: DOI:10.1152/ajpcell.00469.2008

Oxidative stress contributes significantly to the migration of vascular smooth muscle cells (VSMCs), the major pathogenic process of vascular diseases, but the mechanism remains unclear. In the present study, we explored the role of peroxisome proliferator-activated receptor-gamma coactivator-1alpha (PGC-1alpha), a major regulator of mitochondrial biogenesis and energy balance, in VSMC migration in vitro and in vivo. Overexpression of PGC-1alpha in cultured VSMCs led to 74.5% reduction of migration activity and mitochondrial reactive oxygen species (ROS) generation by the increased expression of anti-oxidative proteins such as superoxide dismutase-2 (SOD-2) in the mitochondria. The knockdown of PGC-1alpha by specific small interfering RNA (siRNA) markedly augmented VSMC migration activity and greatly reduced mitochondrial anti-oxidative protein expression. Furthermore, knockdown of SOD-2 expression by siRNA greatly reversed the inhibitory effect of PGC-1alpha overexpression on VSMC migration. In a rat carotid balloon-injury model, adenovirus-mediated overexpression of PGC-1alpha greatly reduced neointimal formation (ratio of intima to media 0.78 +/- 0.09 vs. 1.45 +/- 0.18 in the Ad-GFP group). Moreover, the expression of SOD-2 was significantly increased in vivo in local vessels after injury in the PGC-1alpha-overexpression group. These data strongly suggest that PGC-1alpha inhibits VSMC migration and neointimal formation after vascular injury in rats, mainly by upregulating the expression of the mitochondrial antioxidant enzyme SOD-2. Key words: Restenosis, Antioxidants, Smooth muscle cells, Metabolic syndrome.


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CRRD Object Information
CRRD ID: 2311405
Created: 2009-07-13
Species: All species
Last Modified: 2009-07-13
Status: ACTIVE


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