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首页> 外文期刊>American Journal of Physiology >PGC-1alpha attenuates neointimal formation via inhibition of vascular smooth muscle cell migration in the injured rat carotid artery.
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PGC-1alpha attenuates neointimal formation via inhibition of vascular smooth muscle cell migration in the injured rat carotid artery.

机译：PGC-1alpha通过抑制受伤的大鼠颈动脉中的血管平滑肌细胞迁移来减弱新内膜形成。

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摘要

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 a 74.5% reduction of migration activity and mitochondrial ROS generation by the increased expression of antioxidative proteins such as SOD-2 in the mitochondria. The knockdown of PGC-1alpha by specific small interfering (si)RNA markedly augmented VSMC migration activity and greatly reduced mitochondrial antioxidative 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 adenovirus + green fluorescent protein gene- transfected group). Moreover, the expression of SOD-2 was significantly increased in vivo in local vessels after injury in the PGC-1alpha-overexpressing 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.
机译：氧化应激对血管平滑肌细胞（VSMC）的迁移做出了重要贡献，而血管平滑肌细胞是血管疾病的主要致病过程，但其机制尚不清楚。在本研究中，我们探讨了过氧化物酶体增殖物激活受体-γ共激活因子-1alpha（PGC-1alpha），线粒体生物发生和能量平衡的主要调节剂，在体外和体内VSMC迁移中的作用。培养的VSMC中PGC-1alpha的过表达导致线粒体中抗氧化蛋白（如SOD-2）的表达增加，从而导致迁移活性和线粒体ROS生成减少了74.5％。特定的小干扰（si）RNA抑制PGC-1alpha显着增强了VSMC迁移活性，并大大降低了线粒体抗氧化蛋白的表达。此外，通过siRNA抑制SOD-2表达可以大大逆转PGC-1alpha过表达对VSMC迁移的抑制作用。在大鼠颈动脉球囊损伤模型中，腺病毒介导的PGC-1alpha的过表达大大减少了新内膜的形成（内膜与培养基的比例：腺病毒+绿色荧光蛋白基因转染组的0.78 +/- 0.09与1.45 +/- 0.18 ）。此外，在PGC-1α过表达组中，损伤后体内局部血管中SOD-2的表达显着增加。这些数据强烈表明，PGC-1alpha抑制大鼠血管损伤后VSMC迁移和新内膜形成，主要是通过上调线粒体抗氧化酶SOD-2的表达来实现的。

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