MicroRNA-145 hinders carotid plaque growth via suppression of tumor growth factor-β receptor type II and autophagy.

Abstract

Plaque erosion is increasingly recognized as a critical pathological mechanism in acute coronary syndrome. In this study, we found that microRNA-145 (miR-145) levels were significantly reduced in plaques with grade III-IV stenosis compared with controls. Using an apoE-/- mouse model fed a high-cholesterol diet, we demonstrated that inhibition of miR-145 with antagomiR-145 increased plaque volume and elevated LC3-II expression, a marker of autophagy. Transmission electron microscopy further confirmed a greater abundance of autophagosomes in carotid atherosclerotic plaques from antagomiR-145-treated mice. Mechanistically, miR-145 suppressed both transforming growth factor-β receptor type II (TGFβR-II) expression and autophagy in vascular smooth muscle cells (VSMCs). Silencing TGFβR-II with specific siRNA recapitulated the effects of antagomiR-145 in cultured VSMCs and in vivo. Collectively, these findings suggest that miR-145 may protect against carotid plaque progression by downregulating TGFβR-II and limiting autophagy.