PMID: 26885264Feb 18, 2016Paper

Up-regulation of microRNA-135a protects against myocardial ischemia/reperfusion injury by decreasing TXNIP expression in diabetic mice

American Journal of Translational Research
Hong-Jun ZhuJian Xu

Abstract

The heart in diabetic state is sensitive to myocardial ischemia reperfusion (mI/R) injury. In the present study, we investigated the potential mechanisms of modulating mI/R injury in diabetic state. Diabetic db/db mice and control non-diabetic mice were administrated with mI/R injury or sham operation. Mouse atrial-derived cardiac cell line HL-1 subjected to hypoxia-reoxygenation (H/R) was used as in vitro model of I/R injury to the heart. Compared with normal mice, mI/R elevated the levels of myocardial infarct size, apoptosis and TXNIP expression (in mRNA and protein) in diabetic mice. Myocardial miR-135a expression level was reduced in diabetic mice regardless of mI/R treatment or not. MiR-135a overexpression protected myocardial cells from mI/R injury in diabetic mice. In vitro, high glucose incubation contributed to a significant down-regulation of miR-135a and up-regulation of TXNIP in cells with or without H/R treatment. Luciferase reporter assay showed that TXNIP was a target gene of miR-135a. MiR-135a overexpression protected HL-1 cells from H/R injury in high glucose condition, while this effect was reversed by up-regulated TXNIP. miR-135a protects against mI/R injury by decreasing TXNIP expression in diabetic state.

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Apoptosis

Apoptosis is a specific process that leads to programmed cell death through the activation of an evolutionary conserved intracellular pathway leading to pathognomic cellular changes distinct from cellular necrosis