MiR-3646 Promotes Vascular Inflammation and Augments Vascular Smooth Muscle Cell Proliferation and Migration in Progression of Coronary Artery Disease by Directly Targeting RHOH

Coronary artery disease (CAD) is one of the leading causes of mortality and morbidity worldwide and the number of individuals at CAD risk is increasing. To better manage cardiovascular disease, improved tools for risk prediction including the identification of novel accurate biomarkers are needed. MicroRNAs (miRNAs) are small non-coding RNAs that modulate the expression of protein-coding genes at the post-transcription level and their dysregulated expression has been implicated in various pathogenic processes including cardiovascular disease. Circulating miRNAs have been widely recommended as potential biomarkers for many diseases including coronary artery disease. In the present study, we found that miR-3646 was significantly upregulated in the serum samples of CAD patients and in the mice with acute myocardial infarction (AMI) compared with the healthy control group via using quantitative reverse transcription polymerase chain reaction (qRT-PCR). Moreover, the serum levels of miR-3646 were significantly positively correlated with the expression of IL-6 both in CAD patient samples and AMI mice samples. In human THP-1 macrophages, transfection with miR-3646 mimic elevated the expression of IL-6 while silence of miR-3646 suppressed the IL-6 level. Further exploration of the downstream targets of miR-3646 identified that blocking RHOH expression also could upregulate IL-6 expression. In addition, our findings also showed that miR-3646 promoted vascular smooth muscle cell (VSMC) proliferation and migration by targeting RHOH. These results demonstrate that the miR-3646-RHOH axis may serve as a key regulator in the progression of CAD by modulating vascular inflammation and regulating the biologic behaviors of VSMCs.