Social defeat stress induces myocardial injury by modulating inflammatory factors.

Abstract

ObjectivesWe investigated the endoplasmic reticulum (ER) stress markers C/EBP homologous protein (CHOP) and glucose-regulated protein (GRP) 78, as well as the inflammatory factors nuclear factor (NF)-κB and IκBα, to assess how social defeat stress induces myocardial injury. Furthermore, we evaluated the protective effects of the ER stress inhibitor 4-phenylbutyric acid (PBA) on myocardial injury in mice.MethodsAdult mice were divided into control, control + PBA, social defeat, and social defeat + PBA groups. The social defeat and social defeat + PBA groups were exposed to social defeat stress for 10 days. Cardiac tissues from all groups were analyzed after social defeat stress. H9C2 cells were used to detect the role of the ER stress agonist thapsigargin on expression of ER stress and inflammatory markers.ResultsSocial defeat stress promoted apoptosis of cardiomyocytes, increased CHOP, NF-κB and, phospho-NF-κB protein expression, and decreased GRP78 and IκBα protein expression. Moreover, PBA significantly reversed these changes and attenuated thapsigargin-induced increased expression of CHOP and phospho-NF-κB, and decreased IκBα expression in H9C2 cells.ConclusionsSocial defeat stress initiates ER stress, promotes expression of inflammatory factors, and induces myocardial injury. Inhibiting ER stress could protect the myocardium from social defeat stress-induced myocardial injury.