Abstract 096: Secreted miR-27a in Extracellular Vesicles from THP-1 Cells Cause Hypertension by Reduced Angiotensin-(1-7)-Mas Receptor Expression and Function in Artery
Extracellular vesicles (EVs) play important role in various diseases. Essential hypertension is found to be with higher plasma EV concentrations, whether or not the EVs are involved into pathogenesis of hypertension is not known. Our present study found injection of EVs from THP-1 cells, a monocyte cell line, to SD rats increased blood pressure, accompanied with impaired Ang 1-7 mediated vasodilation in mesenteric artery preconstricted with norepinephrine. In EVs treated SD rats, Mas expression and eNOs expression were decreased in mesenteric artery. After treatment of THP-1 cells with LPS, which represents the inflammatory states, LPS-treated EVs worsen Ang 1-7 mediated vasodilative effect, and further increased blood pressure to higher degree. After degradation of RNAs in EVs by Triton X-100 and RNase, the hypertensive effect of EVs was blocked, indicating RNAs play a vital role in this action. Screening studies, including analysis of gene microarray, comparison of plasma microRNA levels between hypertensive and healthy controls, analysis of microRNA changes with LPS, found that miR-27a is a possible candidate. It is interesting to find that the target of miR-27a is Mas, predicted by genetics software. Immunofluorescence study showed EVs could be transferred to the cytosol and nucleus in the receipt cells. Through loss- and gain-of function approaches, we found that miR-27a decreased Mas and eNOS expressions in HUVECs. The transferred miR-27a in EVs is physiological significance, because injection of EVs from miR-27 transfected HEK293 cells increased blood pressure in SD rats, with impaired Ang 1-7 mediated vasodilation preconstricted by norepinephrine. Moreover, the expressions of Mas and eNOS were decreased in the EVs treated rats. Therefore, we conclude that miR-27a in EVs derived from THP-1 cells decreases Mas receptor expression in HUVECs, consequently influences endothelial NO release and impaired Ang 1-7 mediated vasodilative function, which is involved in the pathogenesis of hypertension.
Author Disclosures: X. Zou: None. J. Wang: None. C. Zeng: None.
- © 2014 by American Heart Association, Inc.