Grape seed proanthocyanidins protect cardiomyocytes against hypoxia/reoxygenation injury by attenuating endoplasmic reticulum stress through PERK/eIF2α pathway.

The aim of the present study was to observe the protective effect of grape seed proanthocyanidins (GSPs) against endoplasmic reticulum (ER) stress‑mediated apoptosis caused by hypoxia/reoxygenation (H/R) injury in H9C2 cardiomyocytes along with its potential mechanisms. H9C2 cardiomyocytes underwent hypoxia for 3 h followed by reoxygenation for 3 h. Different doses of GSPs (50, 100 and 200 µg/ml) were administered 30 min before hypoxia. Cell viability was assessed, as well as lactic dehydrogenase (LDH) activity, cell apoptosis rate, expression levels of glucose‑regulated protein 78 (GRP78), C/EBP‑homologous protein (CHOP), protein kinase RNA‑like ER kinase (PERK), and eukaryotic translation initiation factor‑2 (eIF2α) mRNA and protein. The results revealed that GSPs improved cell viability, reduced LDH activity and reduced the apoptosis rate in cells subjected to H/R, and that the protective effect was most significant when 100 µg/ml in GSPs was administered. GSPs treatment also decreased mRNA and protein expression of GRP78, CHOP, eIF2α and the level of the phosphorylated form of PERK. Furthermore, GSPs displayed a similar protective effect to that of established ER stress inhibitor 4‑phenyl butyric acid. In conclusion, the findings of this study suggest that GSPs may protect H9C2 cardiomyocytes from H/R injury by decreasing ER stress‑mediated apoptosis through the suppression of the PERK/eIF2α signaling pathway.