Significant Role and Mechanism of Microrna-143-3p/klln Axis in the Development of Coronary Heart Disease.

Cardiovascular disease predominantly includes coronary heart disease (CHD) and stroke, results in high morbidity and mortality. MicroRNA-143-3p (miR-143-3p) is a tumor suppressor and is involved in many cancers. However, the role and mechanism of miR-143-3p in coronary heart disease is still unclear. In this study, we identified that miR-143-3p was up-regulated in rabbit CHD model. The results of TargetScan and the dual luciferase reporter assay indicated that KLLN (killin, p53 regulated DNA replication inhibitor) was a direct target of miR-143-3p. Besides, we revealed that KLLN was down-regulated in rabbit coronary heart disease model. In addition, we found that the related-markers of CHD such as TC (total cholesterol), TG (triglyceride), and LDLC (low-density lipoprotein cholesterol) in the model group were significantly increased than that in the control group. And compared with the model group, miR-143-3p inhibitor significantly reduced TC, TG, LDLC expression, while miR-143-3p mimic further increased the expression of TC, TG, and LDLC. We next found that miR-143-3p mimic promoted cell viability and migration of vascular smooth muscle cells, inhibited apoptosis; and these changes were reversed by KLLN-plasmid. And miR-143-3p inhibitor had the counter effects. Our study provided a new target for the treatment of CHD and deserves further study.