Angiotensin-(1-7) Dose-Dependently Inhibits Atherosclerotic Lesion Formation and Enhances Plaque Stability by Targeting Vascular Cells

作者：Yang, Jian Min; Dong, Mei; Meng, Xiao; Zhao, Yu Xia; Yang, Xiao Yan; Liu, Xiao Ling; Hao, Pan Pan; Li, Jing Jing; Wang, Xu Ping; Zhang, Kai; Gao, Fei; Zhao, Xue Qiang; Zhang, Ming Xiang; Zhang, Yun; Zhang, Cheng^*

来源：Arteriosclerosis, Thrombosis, and Vascular Biology, 2013, 33(8): 1978-1985.

DOI：10.1161/ATVBAHA.113.301320

• angiotensin-(1-7)
• angiotensin II
• atherosclerosis
• plaque
• atherosclerotic

Objective @@@ To test the hypothesis that chronic infusion of angiotensin-(1-7) [Ang-(1-7)] may dose-dependently inhibit atherosclerotic lesion formation by targeting vascular smooth muscle cells and a large dose of Ang-(1-7) may stabilize mature plaque by targeting macrophages. @@@ Approach and Results @@@ In vivo, the effects of Ang-(1-7) on atherogenesis and plaque stability were observed in ApoE(-/-) mice fed a high-fat diet and chronic angiotensin II infusion. In vitro, the effects of Ang-(1-7) on vascular smooth muscle cells' proliferation and migration, and macrophage inflammatory cytokines were examined. Ang-(1-7) dose-dependently attenuated early atherosclerotic lesions and inhibited vascular smooth muscle cells' proliferation and migration via suppressing extracellular regulated protein kinase/P38 mitogen-activated protein kinase and janus kinase/signal transducers and activators of transcription activities and enhancing smooth muscle 22 and angiotensin II type 2 receptor expression. Ang-(1-7) treatment resulted in high contents of collagen and vascular smooth muscle cells, and low contents of macrophages and lipids in carotid mature plaques. Ang-(1-7) lowered the expression levels of proinflammatory cytokines and activities of matrix metalloproteinases in mature plaques. @@@ Conclusions @@@ Ang-(1-7) treatment inhibits early atherosclerotic lesions and increases plaque stability in ApoE(-/-) mice, thus providing a novel and promising approach to the treatment of atherosclerosis.

• 出版日期2013-8
• 单位山东大学