Intermittent hypoxia ameliorates myocardial endoplasmic reticulum stress in infarcted mice via the p300/CBP-associated factor (PCAF) pathway

Abstract

Abstract Myocardial infarction (MI) is a common and frequent cardiovascular disease and its treatment is a major challenge in cardiovascular healthcare. Studies have demonstrated that intermittent hypoxia (IH) has therapeutic protective effects. Endoplasmic reticulum stress (ERS) and P300/CBP-associated factor (PCAF) are closely related to post-MI pathology. However, the effect of IH on ERS after infarction and the involvement of PCAF are unknown. First, 4 weeks of IH intervention was followed by observation of changes in left ventricular ejection fraction (LVEF) and shortening fraction (LVFS), levels of ERS-related proteins, and PCAF expression in the mice heart. Compared to the MI group, there was a significant increase in LVEF and LVFS, a significant decrease in myocardial fibrosis index, and a significant decrease in myocardial PCAF expression was significantly reduced, and ATF6, p-IRE1/IRE1, and CHOP expression was reduced in MI-IH group. Next, Mice were randomly classified into four groups, and the medication group was injected with embelin (PCAF inhibitor) (10mg/kg/d, i.p.). 4 weeks of intervention was followed by the same observations as in part I. Four weeks after intervention, LVEF and LVFS were elevated and myocardial fibrosis index was increased in the MI-IH-EMB group compared with the MI-EMB group; ATF6, p-IRE1/IRE1, and CHOP were decreased; the differences in LVEF, LVFS, myocardial fibrosis, and ERS-associated protein expression were not statistically significant between the MI-EMB group and MI-IH. Our findings suggested that IH inhibits ERS by down-regulating PCAF proteins, thereby exerting a protective effect on the heart.