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- Title
MiR-155 protects against sepsis-induced cardiomyocyte apoptosis via activation of NO/cGMP signaling pathway by eNOS.
- Authors
Yanya Lin; Jianxiong Hu; Jianhui Chen; Shijun Chen; Yangfang Cai; Chengda Lin
- 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, sGCa1 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.
- Subjects
CELLULAR signal transduction; APOPTOSIS; SEPSIS; INTRAPERITONEAL injections; HEART failure
- Publication
Tropical Journal of Pharmaceutical Research, 2022, Vol 21, Issue 9, p1851
- ISSN
1596-5996
- Publication type
Article
- DOI
10.4314/tjpr.v21i9.6