miR-145 IS CRITICAL FOR MODULATION OF VASCULAR SMOOTH MUSCLE CELL PROLIFERATION IN HUMAN CAROTID ARTERY STENOSIS

miR-145 is highly expressed in vascular cells, where it regulates phenotypic switching and vascular homeostasis, but its role in carotid artery stenosis (CAS) is controversial. In the present study, the expression of miR-145 was assessed by real time quantitative reverse transcriptase polymerase chain reaction (qRT-PCR) in human samples (both plasma and/or endarterectomy samples) from patients with symptomatic CAS and in controls without CAS. The mouse carotid artery ligation (CAL) model was used to determine the role of miR-145 on vascular smooth muscle cells in vivo (VSMCs) by using a mimic of or an inhibitor of miR-145. We found that miR-145 expression was significantly reduced in the plasma and plaque from patients with CAS (p<0.01). The expression of miR-145 in the mouse CAL model, as assessed by qRT-PCR, was significantly reduced compared to the carotid arteries of the control group (p<0.01). In vitro, enhancement or inhibition of miR-145 in VSMCs demonstrated that mi R-145 significantly inhibited proliferation of VSMCs (p<0.05); in vivo, enhancement of miR-145 significantly inhibited neointimal formation in the CAL model (p<0.01). These results demonstrate that the expression of miR-145 is reduced in human CAS, miR-145 plays a critical role in CAS by modulation of VSMC proliferation, suggesting that MiR-145 may present a potential therapeutic option for treating CAS.