miR-10b Deficiency Affords Atherosclerosis Resistance

Human vascular endothelial cells (ECs) are categorized into two groups; pro-stenotic (Type-I) and anti-stenotic (Type-II) ECs, and one of the master genes for a stress-induced \"Type-II-to-Type-I\" degeneration is Regulator of G-protein signaling 5 (RGS5). Here we show that miR-10b is a crucial downstream mediator in RGS5-dependent degeneration. We also demonstrated the miR-10bhigh Type-I EC exosome has a trans effect which suppresses anti-proliferative abilities of Type-II ECs. Moreover, we found miR-10b-deficient mice showed a resistance to experimental atherosclerosis, where high-fat-high-cholesterol-diet-fed mice were subjected to partial carotid ligation. Furthermore, we determined the key target of miR-10b was Latent transforming growth factor-{beta} binding protein 1 (LTBP1), which is a regulator of TGF-{beta} signaling. Compatible with a commonly accepted view that TGF-{beta} creates the major growth-inhibitory signal against vascular smooth muscle cells, TGF-{beta} inhibitor treatments abolished anti-proliferative functions of Type-II ECs. Therefore, RGS5/miR-10b/LTBP1/TGF-{beta} axis plays a leading role in quality control of ECs.