Subunit of mitochondria and hypertension control via miRNA

• DOI: 10.18143/jwms_v2i2_2047
• Publication Date: 2016-10-05
• Authors: Huaping Li; Xiaorong Zhang; Feng Wang; Ling Zhou; Zhongwei Yin; Jiahui Fan; Xiang Nie; Peihua Wang; Xiangdong Fu; Chen Chen; Dao Wen Wang
• Keywords: Mitochondrial ROS

Background: Excessive reactive oxygen species (ROS) generated in the mitochondria is known to be a causal event hypertensive cardiomyopathy. Multiple recent studies suggest that nuclear genome-encoded miRNAs are able translocate modulate mitochondrial activities, but medical significance of such new miRNA function has remained unclear. Methods: Expression levels representative proteins mitochondrial subunits and ROS production were detected hearts from Wistar rats and spontaneous rats (SHRs) by Western blotting dihydroethidium (DHE) staining, respectively. By using siRNAs, we identified critical role cytochrome b (mt-Cytb) generation. Next, mt-Cytb was predicted as target miRNA-21 (miR-21) by bioinformatic analysis, followed validations real-time PCR Ago2 immunoprecipitation. Furthermore, mechanisms underlying miR-21 enhanced translation verified polysome analysis. To distinguish from total cultured cells, MitoSOX™ Red 2,7-Dichlorodihydrofluorescein diacetate staining performed H9c2 cells. In addition, circulating determined 100 patients 120 controls. Finally, SHRs treated with rAAV-miR-21 via tail vein, blood pressure monitoring with photoelectric tail-cuff system. Cardiac structure functions assessed echocardiography catheter manometer system. Moreover, ROS various organs DHE staining. Results: We observed marked reduction heart SHRs. Down-regulation siRNA recaptured some key disease features, including elevated production. Through computational prediction, immunoprecipitation found miR-21, which induced showed part compensatory program, directly targeted mt-Cytb, leading transfected Circulating significantly higher than those controls, showing positive correlation pressure. Remarkably, rAAV-mediated delivery sufficient reduce attenuate cardiac hypertrophy Conclusions: Our findings reveal translation, alleviate This observation suggests novel theoretical ground for developing miRNA-based therapeutics against hypertension.