The effect and mechanism of POSTN and its alternative splicing on the apoptosis of myocardial cells in acute myocardial infarction

Abstract

Abstract Background Acute myocardial infarction (AMI) is characterized by high morbidity and mortality, and has no effective treatments. Our study aimed to investigate key molecular targets in the pathogenesis of AMI, and provide new strategy for the treatment. Methods The myocardial ischemia and hypoxia model was constructed by using cardiomyocytes from HL-1 mice. The constructed cardiomyocytes, along with normal cardiomyocyte controls, were transfected with lentiviruses carrying over-expressed POSTN gene (GV492-POSTN-WT), over-expressed POSTN alternative splicing gene (GV492-POSTN-MUT) and negative control (GV492-NC), respectively. Cardiomyocyte proliferation and apoptosis, and the level of proteins related to endoplasmic reticulum stress and apoptosis was examined to explore the effects and mechanisms of POSTN and its alternative splicing on the proliferation and apoptosis of ischemic hypoxic and normal cardiomyocytes. Results Ischemic hypoxic and normal cardiomyocytes transfected with GV492-POSTN-WT showed significantly increased OD value, and significantly decreased apoptosis (p < 0.05), with low expression of elF2α, CHOP, GRP78, ATF4 and BAX and high expression of BCL-2 (p < 0.05). Cardiomyocytes transfected with GV492-POSTN-MUT also showed significantly decreased apoptosis (p < 0.05), however, the expression levels of elF2α, CHOP, GRP78, ATF4, BAX and BCL-2 showed no difference between the 2 groups. Conclusion POSTN could promote the proliferation whilst inhibit the apoptosis of normal and ischemic hypoxic cardiomyocytes. The mechanism by which POSTN inhibits cardiomyocyte apoptosis may be through inhibiting the GRP78-eIF2α-ATF4-CHOP pathway of endoplasmic reticulum stress. The alternative splicing of POSTN could also inhibit cardiomyocyte apoptosis, however the mechanism requires further investigation. Our results demonstrated that POSTN might be a potential therapeutic target for AMI.