EXPERIMENTAL RESEARCH
mRNA-103 inhibition attenuates autophagy and inflammation in myocardial infarction by regulating the TLR4 pathway
More details
Hide details
1
A1School of Life Science, Northwest University, Xian, China
2
Department of Vascular Surgery, General Hospital of PLA, Beijing, China
3
Department of Cardiology, Affiliated Hospital of Northwest University, Xian, China
4
Department of Cardiology, Xian No. 3 Hospital, Xian, China
5
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, College of Life Science, Northwest University, Xian, China
6
School of Life Science, Beijing Institute of Technology, Beijing, China
Submission date: 2019-11-09
Final revision date: 2020-01-15
Acceptance date: 2020-01-31
Online publication date: 2020-02-25
KEYWORDS
TOPICS
ABSTRACT
Introduction:
This investigation determined the cardioprotective activity of mRNA-103 inhibitor against myocardial infarction (MI) and also evaluated its molecular mechanism.
Material and methods:
MI was induced in rats by inducing myocardial ischaemia/reperfusion (I/R), and left ventricular (LV) mRNA-103 (1 × 107 TU) was injected into the myocardium around the infarcted area. The effect of mRNA-103 inhibitor was assessed by determining the levels of myocardial enzymes and cytokines in the serum, the myeloperoxidase (MPO) activity, and the levels of Toll-like receptor 4 (TLR4), nuclear factor κ-light-chain enhancer of activated B cells (NF-κB), and MyD88 mRNAs in the myocardial tissues of MI rats. Immunocytochemical analysis and a histopathology study were also performed.
Results:
The levels of myocardial enzymes and cytokines were lower in the mRNA-103 inhibitor-treated group than in the group in which the only treatment was the induction of MI. There was a lower percentage of infarcted area and a lower apoptosis index in the mRNA-103 inhibitor-treated group compared to the MI-only. The levels of TLR4, NF-B, and MyD88 mRNAs were lower in the myocardial tissues of the mRNA-103 inhibitor-treated group than in the MI-only group. Immunohistochemical analysis revealed that treatment with mRNA-103 inhibitor ameliorated the expression of TLR4 in the myocardial tissues of MI rats.
Conclusions:
The data revealed that inhibition by mRNA-103 protects against myocardial injury in MI rats by regulating the inflammasome pathway.