Social defeat stress induces myocardial injury by modulating inflammatory factors

Objectives: We 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. Methods: Adult 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. Results: Social 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. Conclusions: Social 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.