Atorvastatin protects cardiac progenitor cells from hypoxia-induced cell growth inhibition via MEG3/miR-22/HMGB1 pathway.

Heart failure (HF) induced by ischemia myocardial infarction (MI) is one of the major causes of morbidity and mortality all around the world. Atorvastatin, a hydroxymethylglutaryl coenzyme A reductase inhibitor, has been demonstrated to benefit patients with ischemic or non-ischemic-induced HF, but the mechanism is still poorly understood. Increasing evidence indicates that lncRNAs play important role in variety of human disease. However, the role and underlying molecular mechanisms remain largely unclear. In our work, we applied 0.5% O2 to generate a hypoxia cardiac progenitor cell (CPC) model. Then, CCK8 and EdU assays were employed to investigate the role of atorvastatin in hypoxia CPC cell model. We found that hypoxia inhibits CPC viability and proliferation through modulating MEG3 expression, while atorvastatin application can protect CPCs from hypoxia-induced injury through inhibiting MEG3 expression. Then, we demonstrated that repression of MEG3 inhibited the hypoxia-induced injury of CPCs and overexpression of MEG3 inhibited the protective effect of atorvastatin in the hypoxia-induced injury of CPCs. Furthermore, our study illustrated that atorvastatin played its role in CPC viability and proliferation by modulating the expression of HMGB1 through the MEG3/miR-22 pathway. Our study, for the first time, uncovered the molecular mechanism of atorvastatin's protective role in cardiomyocytes under hypoxia condition, which may provide an exploitable target in developing effective therapy drugs for MI patients.