Lycopene restores the effect of ischemic postconditioning on myocardial ischemia‑reperfusion injury in hypercholesterolemic rats.
Int J Mol Med. 2019 Jun ;43(6):2451-2461. Epub 2019 Apr 15. PMID: 31017253
Ischemic postconditioning (IPoC) has been demonstrated to prevent myocardial ischemia‑reperfusion injury (MIRI), but its cardioprotective effect is abrogated by hypercholesterolemia. The aim of the present study was to determine whether lycopene (LP), a type of carotenoid, can restore the cardioprotective effect of IPoC in hypercholesterolemic rats. Male Wistar rats were fed a cholesterol‑enriched diet for 12 weeks to establish a hypercholesterolemic model. The rat hearts were isolated and subjected to 30 min ischemia and 60 min reperfusion using a Langendorff apparatus. LP was administered to the rats intraperitoneally for 5 consecutive days prior to ischemia and reperfusion. Myocardial pathological changes, infarct size and cell apoptosis were measured by hematoxylin and eosin, triphenyltetrazolium chloride and TUNEL staining, respectively. The changes in endoplasmic reticulum (ER) stress markers, the reperfusion injury salvage kinase (RISK) pathway and mitochondrial apoptosis‑related proteins were detected by western blotting. Overall, the results demonstrated that low‑dose LP in combination with IPoC ameliorated myocardial histopathological changes, reduced the infarct size and release of cardiac enzymes, and decreased cardiomyocyte apoptosis in hypercholesterolemic rats, but no beneficial effects were achieved by the same dose of LP or IPoC treatment were used alone. Furthermore, the combination of LP and IPoC inhibited the expression of glucose‑regulated protein 78 and C/EBP homologous protein, increased the phosphorylation levels of AKT, ERK1/2 and glycogen synthase kinase‑3β, repressed mitochondrial permeability transition pore opening, and reduced the expression of cytochrome c, cleaved caspase‑9 and cleaved caspase‑3. Collectively, these findings demonstrated that LP can restore the cardioprotective effects of IPoC on MIRI inhypercholesterolemic rats, and this restoration by LP was mediated by inhibition of ER stress and reactivation of the RISK pathway in hypercholesterolemic rat myocardium.