Abstract 9191: MicroRNA-150 is Essential in the Regulation of Blood Pressure

Abstract

Background & Hypothesis. Micro RNAs are small noncoding RNAs that regulate protein expression at the post-transcriptional level. The purpose of this study was to determine if microRNA-150 (miR-150) plays a role in the regulation of blood pressure (BP). Methods & Results. We found that knockout of miR-150 resulted in a significant increase in systolic, diastolic and mean BP in mice. Vascular relaxing responses to acetylcholine were decreased significantly in miR-150 knockout (miR150-KO) mice, suggesting impaired endothelial function. Therefore, miR-150 is essential in the maintenance of normal BP and endothelial function. MiR150-KO was accompanied by a significant increase in NADPH oxidase activity and superoxide production in aortas and kidneys. MiR150-KO mice demonstrated vascular and renal remodeling. Interestingly, miR150-KO significantly increased Cyp11β2 protein expression in adrenal cortex, suggesting that miR-150 is a negative regulator of Cyp11β2. Plasma level of aldosterone was elevated in the miR150-KO mice. It was noted that daily treatment with aldosterone receptor blockade eplerenone (EPL) effectively reversed hypertension, endothelial dysfunction, increases in NADPH oxidase activity and superoxide production, and vascular and renal damage in miR150-KO mice. Conclusions. These results suggest that miR150-KO-inudced hypertension may be mediated by the upregulation of Cyp11β2 expression which led to increased biosynthesis of aldosterone. It is concluded that miR-150 is a critical regulator of Cyp11β2 in the control of BP. MiR-150 may be a novel therapeutic target for hypertension. (Supported by NIH R01 HL105362).