The ischemia-enhanced lncRNA MIPRL protects against acute myocardial infarction by reducing cardiac cell apoptosis and improving cardiac function through the stabilization of HSPB8 mRNA.
The lncRNA MIPRL protects against acute myocardial infarction by stabilizing HSPB8 mRNA and reducing cardiomyocyte apoptosis, identifying it as a potential therapeutic target.
ncRNA 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.
吴等人（Mon，）对急性心肌梗死进行了研究。评估了MIPRL过表达或敲除与野生型或Ad-GFP对照在心肌梗死大小、心脏功能和细胞凋亡方面的影响。缺血增强的lncRNA MIPRL通过减少心脏细胞凋亡和改善心脏功能来保护心脏免受急性心肌梗死的影响，这一过程与HSPB8 mRNA的稳定有关。