Stress-enhanced cardiac lncRNA morrbid protects hearts from acute myocardial infraction

• Published in: JCI insight 2023-07
• Main Authors: Yu, Yang, Yang, Haiqiong, Li, Qiuting, Ding, Nianhui, Gao, Jiali, Qiao, Gan, Feng, Jianguo, Zhang, Xin, Wu, Jianming, Yu, Yajun, Zhou, Xiangyu, Wang, Xiaobin, Zhang, Chunxiang
• Format: Article
• Language: English
• ISSN: 2379-3708

Morrbid is a new identified leukocyte-specific long noncoding RNA (lncRNA). However, the expression and biological functions of Morrbid in cardiomyocytes and in heart disease are currently unclear. The study is to determine the roles of cardiac Morrbid in acute myocardial infarction (AMI) and to identify the potential cellular and molecular mechanisms involved. We found that both human and mouse cardiomyocytes could express a significant amount of Morrbid and its expression was increased in cardiomyocytes with hypoxia or oxidative stress, and in mouse hearts with AMI. Overexpression of Morrbid reduced the myocardial infarct size and cardiac dysfunction, whereas the infarct size and cardiac dysfunction were deteriorated in cardiomyocyte-specific Morrbid knockout (Morrbidfl/fl/Myh6-Cre) mice. We identified that Morrbid had a protective effect against hypoxia or H2O2-induce apoptosis, which was also confirmed in vivo in mouse hearts after AMI. We further discovered that serpine1 was a direct target gene of Morrbid, which was involved in Morrbid-mediated protective effect on cardiomyocytes. In summary, we have found for the first time that the cardiac Morrbid is a stress-enhanced lncRNA, which protects hearts from AMI via anti-apoptosis through its target gene serpine1. Morrbid may be a novel promising therapeutic target for ischemic heart diseases such as AMI.