通过靶向血管细胞剂量依赖性血管紧张素 - (1-7)可抑制动脉粥样硬化病灶的形成和增强斑块的稳定性
Abstract
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 22α 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. © 2013 American Heart Association, Inc.
来源: Scopus
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