Protective Effect of Peroxisome Proliferator-Activated Receptor α Activation against Cardiac Ischemia-Reperfusion Injury Is Related to Upregulation of Uncoupling Protein-3

الملخص EN

Activation of peroxisome proliferator-activated receptor α (PPARα) confers cardioprotection, while its mechanism remains elusive.

We investigated the protective effect of PPARα activation against cardiac ischemia-reperfusion injury in terms of the expression of uncoupling protein (UCP).

Myocardial infarct size and UCP expression were measured in rats treated with WY-14643 20 mg/kg, a PPARα ligand, or vehicle.

WY-14643 increased UCP3 expression in vivo.

Myocardial infarct size was decreased in the WY-14643 group (76 ± 8% versus 42 ± 12%, P<0.05).

During reperfusion, the incidence of arrhythmia was higher in the control group compared with the WY-14643 group (9/10 versus 3/10, P<0.05).

H9c2 cells were incubated for 24 h with WY-14643 or vehicle.

WY-14643 increased UCP3 expression in H9c2 cells.

WY-14643 decreased hypoxia-stimulated ROS production.

Cells treated with WY-14643 were more resistant to hypoxia-reoxygenation than the untreated cells.

Knocking-down UCP3 by siRNA prevented WY-14643 from attenuating the production of ROS.

UCP3 siRNA abolished the effect of WY-14643 on cell viability against hypoxia-reoxygenation.

In summary, administration of PPARα agonist WY-14643 mitigated the extent of myocardial infarction and incidence of reperfusion-induced arrhythmia.

PPARα activation conferred cytoprotective effect against hypoxia-reoxygenation.

Associated mechanisms involved increased UCP3 expression and resultant attenuation of ROS production.