miR-1929-3p Overexpression Alleviates Murine Cytomegalovirus-Induced Hypertensive Myocardial Remodeling by Suppressing EdnraNLRP3 Inflammasome Activation

Abstract EN

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.