The ischemia-enhanced myocardial infarction protection-related lncRNA protects against acute myocardial infarction

Long non-coding RNA RP11-64B16.4 (myocardial infarction protection-related lncRNA [MIPRL]) is among the most abundant and the most upregulated lncRNAs in ischemic human hearts. However, its role in ischemic heart disease is unknown. We found MIPRL was conserved between human and mouse and its expression was increased in mouse hearts after acute myocardial infarction (AMI) and in cultured human and mouse cardiomyocytes after hypoxia. The infarcted size, cardiac cell apoptosis, cardiac dysfunction, and cardiac fibrosis were aggravated in MIPRL knockout mice after AMI. The above adverse results could be reversed by re-expression of MIPRL via adenovirus expressing MIPRL. Both in vitro and in vivo, we identified that heat shock protein beta-8 (HSPB8) was a target gene of MIPRL, which was involved in MIPRL-mediated anti-apoptotic effects on cardiomyocytes. We further discovered that MIPRL could combine with the messenger RNA (mRNA) of HSPB8 and increase its expression in cardiomyocytes by enhancing the stability of HSPB8 mRNA. In summary, we have found for the first time that the ischemia-enhanced lncRNA MIPRL protects against AMI via its target gene HSPB8. MIPRL might be a novel promising therapeutic target for ischemic heart diseases such as AMI. Myocardial infarction protection-related lncRNA (MIPRL) expression is increased in hearts after acute myocardial infarction (AMI) and in cultured cardiomyocytes after hypoxia. The upregulated MIPRL increases the expression of heat shock protein beta-8 (HSPB8) by enhancing the stability of HSPB8 messenger RNA. MIPRL protects against AMI via HSPB8-mediated inhibition of cardiac cell apoptosis and necrosis during AMI. image