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

Abstract

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.

• Authors: Jinwen Su, Ming Fang, Bei Tian, Jun Luo, Can Jin, Xuejun Wang, Zhongping Ning, Xinming Li
• Journal: Acta biochimica et biophysica Sinica (Acta Biochim Biophys Sin (Shanghai)) Vol. 50 Issue 12 Pg. 1257-1265 (Dec 01 2018) ISSN: 1745-7270 [Electronic] China
• PMID: 30481260 (Publication Type: Journal Article)

Chemical References

• Cardiotonic Agents
• HMGB1 Protein
• Hydroxymethylglutaryl-CoA Reductase Inhibitors
• MEG3 non-coding RNA, human
• MIRN22 microRNA, human
• MicroRNAs
• RNA, Long Noncoding
• Atorvastatin

Topics

• Animals
• Atorvastatin (pharmacology)
• Base Sequence
• Cardiotonic Agents (pharmacology)
• Cell Hypoxia
• Cell Proliferation (drug effects, genetics)
• Cell Survival (drug effects, genetics)
• Cells, Cultured
• Gene Expression (drug effects)
• HMGB1 Protein (genetics, metabolism)
• Hydroxymethylglutaryl-CoA Reductase Inhibitors (pharmacology)
• Mice, Inbred C57BL
• MicroRNAs (genetics)
• Myoblasts, Cardiac (cytology, drug effects, metabolism)
• RNA, Long Noncoding (genetics)
• Sequence Homology, Nucleic Acid