Periostin renders cardiomyocytes vulnerable to acute myocardial infarction via pro-apoptosis.

AIMS

As a severe cardiovascular disease, acute myocardial infarction (AMI) could trigger congestive heart failure. Periostin (Postn) has been elucidated to be dramatically up-regulated in myocardial infarction. Abundant expression of Postn was also observed in the infarct border of human and mouse hearts with AMI. This work is dedicated to explore the mechanism through which Postn exerts its functions on AMI.

METHODS AND RESULTS

The expression of Postn in AMI mice and hypoxia-treated neonatal mouse cardiomyocytes (NMCMs) was quantified by qRT-PCR. The biological functions of Postn in AMI were explored by trypan blue, TUNEL, flow cytometry analysis, and JC-1 assays. Luciferase activity or MS2-RIP or RNA pull-down assay was performed to study the interaction between genes. Postn exhibited up-regulated expression in AMI mice and hypoxia-treated NMCMs. Functional assays indicated that cell apoptosis in NMCMs was promoted via the treatment of hypoxia. And Postn shortage could alleviate cell apoptosis in hypoxia-induced NMCMs. Postn was verified to bind to mmu-miR-203-3p and be down-regulated by miR-203-3p overexpression. Postn and miR-203-3p were spotted to coexist with small nucleolar RNA host gene 8 (Snhg8) in RNA-induced silencing complex. The affinity between Snhg8 and miR-203-3p was confirmed. Afterwards, Snhg8 was validated to promote cell apoptosis in hypoxia-induced NMCMs partially dependent on Postn. Furthermore, vascular endothelial growth factor A (Vegfa) was revealed to bind to miR-203-3p and be implicated in the Snhg8-mediated AML cell apoptosis and angiogenesis.

CONCLUSIONS

miR-203-3p availability is antagonized by Snhg8 for Postn and Vegfa-induced AMI progression.