Effect of Endoplasmic Reticulum Stress and Autophagy in the Regulation of Post-infarct Cardiac Repair

Abstract

Acute myocardial infarction (AMI) is reported to be accompanied by endoplasmic reticulum (ER) stress and autophagy induction. Nevertheless, the roles of ER stress and autophagy in post-infarct reparative fibrosis remain to be elucidated. To investigate the effects of ER stress and autophagy on the regulation of post-infarct reparative fibrosis. The expression of GRP78 and LC3 in cardiac fibroblasts in human heart tissues obtained from patients with or without AMI was assessed by immunofluorescence. Invitro, human cardiac fibroblasts (HCFs) were stimulated by various agents, the expression of GRP78, LC3 and fibronectin in these was evaluated by immunoblot and/or immunofluorescence. After AMI, HCFs expressed significantly higher levels of GRP78 and LC3. ER stress inducer, tunicamycin (200ng/mL) significantly increased the level of autophagy and reduced expression of fibronectin in HCFs, both of which were reversed by 4 Phenylbutyric acid. Under the condition of ER stress, the expression of fibronectin in HCFs was regulated by different levels of autophagy. LC3 co-localized with fibronectin when stimulated HCFs with tunicamycin. AMI induces ER stress in cardiac fibroblasts, down-regulating fibronectin via enhanced autophagy. These findings suggest that ER stress and autophagy may be a therapeutic target to improve prognosis of patients with AMI.