期刊
JOURNAL OF HYPERTENSION
卷 28, 期 8, 页码 1646-1654出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1097/HJH.0b013e32833a4922
关键词
endothelin-1; microRNA; vascular endothelial cells
资金
- National Basic Research Program of China (973 Program [2009CB521900]
- Shanghai Key Natural Science Fund [08431900300]
- National Natural Science Funds of China [30672455, 30973526]
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 30 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. J Hypertens 28: 1646-1654 (c) 2010 Wolters Kluwer Health vertical bar Lippincott Williams & Wilkins.
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