Angiotensin-(1–7) Dose-Dependently Inhibits Atherosclerotic Lesion Formation and Enhances Plaque Stability by Targeting Vascular Cells
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 ERK/P38 and JAK/STAT activities and enhancing SM22α and AT2R 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.
- Received February 22, 2012.
- Accepted May 13, 2013.
- © 2013 American Heart Association, Inc.