Alteration in microRNA-25 expression regulate cardiac function via renin secretion.

Abstract

Heart failure arises from diverse cardiovascular diseases, including hypertension, ischemic disease and atherosclerosis, valvular insufficiency, myocarditis, and contractile protein mutations. MicroRNAs are dysregulated in heart failure, but identification of the specific microRNAs involved remains incomplete. Here, we evaluate miR-25 expression in the peripheral blood from healthy, dilated cardiomyopathy (DCM), remote infarct (OMI), hypertensive heart disease (HHD), and HHD resulting in heart failure (HHDF) using q-PCR. Interestingly, we discovered miR-25 expression in humans is initially decreased at the onset of heart failure but is later increased in end-stage heart failure. We also show that overexpression of miR-25 in normal mice causes cardiomyocyte fibrosis and apoptosis. However, inhibition of miR-25 in normal mice led to activate renin-angiotensin system (RAS) and high blood pressure, mild heart dilation. Notably, the miR-25 cluster knock-out mice was also characterized high blood pressure and no obvious cardiac function alteration. RNA sequencing showed the alteration of miR-25 target genes in angomir-treated mice, including the renin secretion signal related gene. In vitro, cotransfection with the miR-25 antagomir repressed luciferase activity from a reporter construct containing the Pde3a and Cacnalc untranslated region. In summary, miR-25 expression during different stages of heart disease, offers a new perspective for the role of miR-25 function in heart failure.

• Authors: Hongzhi Li, Yeming Xie, Yunshuang Liu, Yali Qi, Chong Tang, Xuefeng Li, Kuiyang Zuo, Dingce Sun, Yongchao Shen, Daxin Pang, Yanhui Chu, Binghai Zhao
• Journal: Experimental cell research (Exp Cell Res) Vol. 365 Issue 1 Pg. 119-128 (04 01 2018) ISSN: 1090-2422 [Electronic] United States
• PMID: 29499204 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2018 Elsevier Inc. All rights reserved.

Chemical References

• MicroRNAs
• Cyclic Nucleotide Phosphodiesterases, Type 3
• Renin

Topics

• Aged
• Animals
• Apoptosis (physiology)
• Cardiomyopathy, Dilated (metabolism)
• Cyclic Nucleotide Phosphodiesterases, Type 3 (metabolism)
• Female
• Fibrosis (metabolism)
• Heart Failure (metabolism)
• Humans
• Hypertension (metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• MicroRNAs (metabolism)
• Middle Aged
• Myocardium (metabolism)
• Myocytes, Cardiac (metabolism)
• Renin (metabolism)
• Renin-Angiotensin System (physiology)