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 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 resu...