Tropical Journal of Pharmaceutical Research

Original Research Article | OPEN ACCESS

MiR-155 protects against sepsis-induced cardiomyocyte apoptosis via activation of NO/cGMP signaling pathway by eNOS

Yanya Lin¹, Jianxiong Hu¹, Jianhui Chen¹, Shijun Chen¹, Yangfang Cai¹, Chengda Lin²

; ¹Critical Care Medicine, Affiliated Hospital of Putian University, Putian, Fujian 351100, China;

For correspondence:- Chengda Lin Email: linmlmx666@163.com

Accepted: 27 August 2022 Published: 30 September 2022

Citation: Lin Y, Hu J, Chen J, Chen S, Cai Y, Lin C. MiR-155 protects against sepsis-induced cardiomyocyte apoptosis via activation of NO/cGMP signaling pathway by eNOS. Trop J Pharm Res 2022; 21(9):1851-1858 doi: 10.4314/tjpr.v21i9.6

© 2022 The authors.
This is an Open Access article that uses a funding model which does not charge readers or their institutions for access and distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0) and the Budapest Open Access Initiative (http://www.budapestopenaccessinitiative.org/read), which permit unrestricted use, distribution, and reproduction in any medium, provided the original work is properly credited..

Abstract

Purpose: To examine the impact of miR-155 on sepsis-induced myocardial apoptosis and heart failure, and to explore its molecular mechanism.

Methods: Mice were divided into four groups and septic myocardial dysfunction was induced by intraperitoneal injection of lipopolysaccharide (LPS, 5 mg/kg). The LPS stimulation expression of miR-155 levels was determined by real time-polymerase chain reaction (RT-PCR). In vivo, echocardiography and TUNEL staining were used to investigate the effects of miR-155 in inhibiting cardiac function and myocardial apoptosis. Changes in the expression of eNOS when miR-155 was overexpressed or inhibited were determined by RT-PCR, while double luciferase gene assay assessed the relationship between eNOS and miR-155, eNOS, expression of iNOS, SGC alpha 1, and PKG protein.

Results: MiR-155 was significantly increased after LPS stimulation (p < 0.01). In vitro, the inhibition of miR-155 by antagomiR significantly down-regulated the apoptosis of cardiomyocytes (p < 0.05), while overexpression of miR-155 by agomiR significantly up-regulated the apoptosis of cardiomyocytes (p < 0.05). In vivo, ejection fraction, fractional shortening and heart weight were significantly increased (p < 0.05), while apoptosis was significantly decreased (p < 0.05). MiR-155 negatively regulated the expression of eNOS (p < 0.01), and targeted the expression of eNOS mRNA (p < 0.001). In addition, the expression of eNOS, sGCα1 and PKA were significantly up-regulated (p < 0.05), while the expression of iNOS was significantly down-regulated (p < 0.05) after the inhibition of miR-155 in LPS mouse model.

Conclusion: MiR-155 regulates sepsis-induced cardiomyocyte apoptosis and heart failure through eNOS /NO/cGMP signaling pathway. Thus, these findings can potentially facilitate the development of an effective strategy for management of heart failure.

Keywords: Apoptosis, Cardiac dysfunction, miRNA-155, Sepsis