Arginase I enhances atherosclerotic plaque stabilization by inhibiting inflammation and promoting smooth muscle cell proliferation

作者：Wang, Xu-Ping; Zhang, Wei; Liu, Xiao-Qian; Wang, Wen-Ke; Yan, Fei; Dong, Wen-Qian; Zhang, Yun^*; Zhang, Ming-Xiang

来源：European Heart Journal, 2014, 35(14): 911-919.

DOI：10.1093/eurheartj/eht329

• Arginase I
• Atherosclerotic plaque stability
• Inflammation
• Proliferation

The aim of this study was to investigate the effect of Arginase I (ArgI) on plaque stabilization in unruptured atherosclerotic plaque and explore its mechanism. @@@ The atherosclerotic plaque model was established in New Zealand rabbits by balloon injury of abdominal arteries and a high cholesterol (1) diet. Arginase I overexpression reduced the content of macrophages and lipids and increased that of smooth muscle cells and collagen in the atherosclerotic plaque, thus contributing to decreased plaque vulnerability. Arginase I overexpression decreased the expression of the inflammatory cytokines tumour necrosis factor- (TNF-) and interleukin-6 (IL-6) as well as inducible nitric oxide synthase (iNOS) in plaques. In vitro, ArgI overexpression or iNOS inhibition abolished the secretion of TNF- and IL-6 induced by lipopolysaccharide in Raw264.7 cells. However, exogenous l-arginine restored the expression of inflammatory cytokines. Arginase I overexpression inhibited the activity of iNOS without changing its expression. Moreover, ArgI co-localized with iNOS in both Raw264.7 cells and human aortic atherosclerotic plaques. In addition, the IL-10 level was increased in plaque with ArgI overexpression. Finally, ArgI promoted aortic vascular smooth muscle cell proliferation, which was associated with increased production of intracellular polyamines. @@@ ArgI enhances the stability of atherosclerotic plaque by inhibiting the expression of inflammatory cytokines and stimulating smooth muscle cell proliferation.

• 出版日期2014-4
• 单位山东大学