Rosuvastatin Reverses Hypertension-Induced Changes in the Aorta Structure and Endothelium-Dependent Relaxation in Rats Through Suppression of Apoptosis and Inflammation

瑞舒伐他汀通过抑制细胞凋亡和炎症逆转高血压引起的大鼠主动脉结构变化和内皮依赖性舒张

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作者:Qingbo Lv, Yao Wang, Ya Li, Liding Zhao, Yingchao Gong, Meihui Wang, Min Wang, Guosheng Fu, Wenbin Zhang

Abstract

Vascular remodeling is one of the most critical complications caused by hypertension. Previous studies have demonstrated that rosuvastatin has anti-inflammatory, antioxidant, and antiplatelet effects and therefore can be used to treat cardiovascular disease. In this study, we explored the beneficial effects of rosuvastatin in reversing aortic remodeling in spontaneously hypertensive rats. After treating with different doses of rosuvastatin, its antilipid, antiapoptosis, and anti-inflammatory effects were determined. We also examined whether rosuvastatin can improve the structure and function of the aorta. We found that rosuvastatin treatment of spontaneously hypertensive rats for 2 months at 2 different doses can effectively reduce the media thickness of the aorta compared with the control group. Similarly, rosuvastatin improved the vascular relaxation function of the aortic rings at a high level of acetylcholine in vitro. Mechanistically, it was found that rosuvastatin increased the expression of endothelial nitric oxide synthase and plasma nitrite/nitrate levels. Besides, rosuvastatin suppressed the apoptosis and inflammation and upregulated the expression of gap-junction complex connexin 43 both in media and endothelium. Finally, rosuvastatin inhibited the AT1R/PKCα/HSP70 signaling transduction pathway. In summary, these findings demonstrated that rosuvastatin could improve the vascular structure and function mainly by increasing endothelial nitric oxide synthase expression and preventing apoptosis and inflammation. This study provided evidence that rosuvastatin has beneficial effects in reversing the remodeling of the aorta due to hypertension.

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