Korean Circ J.  2020 Mar;50(3):250-263. 10.4070/kcj.2019.0107.

MiR-484 Protects Rat Myocardial Cells from Ischemia-Reperfusion Injury by Inhibiting Caspase-3 and Caspase-9 during Apoptosis

Affiliations
  • 1Department of Internal Medicine, The Graduate School of Jinzhou Medical University, Jinzhou, China.
  • 2Department of Cardiology, The Fourth People's Hospital of Shenyang, Shenyang, China. yinjun2019@163.com

Abstract

BACKGROUND AND OBJECTIVES
To reveal the detail mechanism of miR-484 on myocardial ischemia-reperfusion (MI/R) injury.
METHODS
Rats model of MI/R injury was established based on control (Con; sham operate) group, ischemia-reperfusion (I/R) group, miR-484 treatment (miR) group, and I/R-negative control (IR-C) group, followed by pathological and interleukin (IL)-6, tumor necrosis factor (TNF)-α, and IL-1β expression evaluation. Then the myocardial apoptosis, as well as the expression of miR-484, caspase-3, and caspase-9 in myocardium were examined. Finally, the regulatory relation between miR-484 and SMAD family member 7 (SMAD7) was predicated, followed by verification analysis.
RESULTS
Compared with Con group, the expression of miR-484 in I/R and IR-C group was decreased. Compared with I/R and IR-C group, the expression of miR-484 was increased in miR group. Compared with Con group, the expression levels of IL-6, TNF-α, and IL-1β in cardiac myocytes of I/R group and IR-C group were increased. Compared with Con group, the apoptotic index, membrane potential of I/R, and the expression of caspase-3/9 were increased in IR-C group. Compared with the I/R and IR-C groups, the apoptotic index of myocardial cells in the ischemic region was decreased, the membrane potential was increased, and the expression of caspase-3/9 was decreased significantly in the miR group. SMAD7 was the target gene of miR-484.
CONCLUSIONS
MiR-484 protected myocardial cells from I/R injury by suppressing caspase-3 and caspase-9 expression during cardiomyocyte apoptosis. MiR-484 reduced the expression of IL-6, TNF-α, and IL-1β in MI/R. MiR-484 might alleviate the decreasing of mitochondrial membrane potential in MI/R cells.

Keyword

Apoptosis; Mitochondrial membrane potential; Caspase-3; Caspase-9

MeSH Terms

Animals
Apoptosis*
Caspase 3*
Caspase 9*
Humans
Interleukin-6
Interleukins
Membrane Potential, Mitochondrial
Membrane Potentials
Myocardium
Myocytes, Cardiac
Rats*
Reperfusion Injury*
Tumor Necrosis Factor-alpha
Caspase 3
Caspase 9
Interleukin-6
Interleukins
Tumor Necrosis Factor-alpha
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