MicroRNA-125a/b-5p inhibits endothelin-1 expression in vascular endothelial cells

BACKGROUND: Endothelin-1 (ET-1) is considered to be one of the most potent and long-lasting vasoconstrictive peptides, but the mechanisms on the regulation of ET-1 expression are not fully understood. METHOD AND RESULTS: In this study, we found that microRNA (miR)-125a-5p and miR-125b-5p are highly expressed in vascular endothelial cells (VECs), which can be regulated by oxidized low-density lipoprotein (oxLDL). To explore the function of miR-125a/b-5p in VECs, we examined the roles of potential targets of miR-125a/b-5p that could influence endothelium function. We found that both miR-125a/b-5p can suppress oxLDL-induced ET-1 expression by directly targeting 3' untranslated region of prepro-endothelin-1 (preproET-1) mRNA determined by luciferase reporter assay, western blot, and enzyme immunometric assay. Consistently, inhibitors of miR-125a/b-5p can directly enhance preproET-1 expression. The decreased expressions of miR-125a-5p and miR-125b-5p are negatively associated with upregulation of preproET-1 expression in aorta of stroke-prone spontaneously hypertensive rats (SHR-SPs). CONCLUSION: Our finding demonstrated that endothelial miR-125a/b-5p inhibits ET-1 expression in VECs, which revealed a novel miRNA-mediated mechanism in vasomotor homeostasis.