1. miR-1929-3p Overexpression Alleviates Murine Cytomegalovirus-Induced Hypertensive Myocardial Remodeling by Suppressing Ednra/NLRP3 Inflammasome Activation.
- Author
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Wang, YongJia, Huang, Zhen, Zhong, Hua, Wang, LaMei, Xi, DongMei, Shi, YunZhong, Zhou, Wei, Liu, YongMin, Tang, Na, and He, Fang
- Subjects
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ANIMAL experimentation , *CYTOMEGALOVIRUSES , *ECHOCARDIOGRAPHY , *ENZYME-linked immunosorbent assay , *HYPERTENSION , *IMMUNOGLOBULINS , *IMMUNOHISTOCHEMISTRY , *INTERLEUKINS , *MICE , *MYOCARDIUM , *RECOMBINANT proteins , *STAINS & staining (Microscopy) , *WESTERN immunoblotting , *MICRORNA , *NATRIURETIC peptides , *VASCULAR remodeling - Abstract
MicroRNAs (miRNAs) play crucial roles in the development of essential hypertension (EH). Previously, we found that the expression of miR-1929-3p was decreased in C57BL/6 mice with hypertension induced by murine cytomegalovirus (MCMV). In this study, we explored the role of miR-1929-3p in hypertension myocardial remodeling in MCMV-infected mice. First, we measured MCMV DNA and host IgG and IgM after infection and determined the expression of miR-1929-3p and its target gene endothelin A receptor (Ednra) mRNA in the myocardium of mice. Then, we performed invasive blood pressure (BP) monitoring. Heart-to-body weight ratio (HW/BW%), along with mRNA levels of B-type natriuretic peptide (BNP) and beta myosin heavy chain (β-MHC), revealed myocardial remodeling. Hematoxylin/eosin and Masson's trichrome staining indicated morphological changes in the myocardium. Cardiac function was assessed via echocardiography. Moreover, MCMV-infected mice were injected with recombinant adeno-associated virus- (rAAV-) miR-1929-3p overexpression vector. Immunohistochemistry and western blotting showed the expression of Ednra and the activation of NOD-like receptor pyrin domain containing 3 (NLRP3) inflammasome. And enzyme-linked immunosorbent assay (ELISA) revealed the concentrations of endothelin-1 (ET-1), interleukin-1β (IL-1β), and interleukin-18 (IL-18). In this study, we found that decreased expression of miR-1929-3p in MCMV-infected mice induced high BP and further development of myocardial remodeling cardiac function injury through increased expression of Ednra. Strikingly, overexpression of miR-1929-3p ameliorated these pathological changes of the heart. The positive effect was shown to be associated with inhibition of NLRP3 inflammasome activation and decreased expression of key proinflammatory cytokine IL-1β. Collectively, these results indicate that miR-1929-3p overexpression may effectively alleviate EH myocardial remodeling by suppressing Ednra/NLRP3 inflammasome activation in MCMV-infected mice. [ABSTRACT FROM AUTHOR]
- Published
- 2020
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