Key result
Transplantation of a cardiac patch overexpressing lncRNA Cmarr significantly reduced infarct size and improved cardiac function in a mouse model of myocardial infarction.
Why the study?
The immature phenotype of embryonic stem cell-derived cardiomyocytes limits their application, and the molecular mechanisms of cardiomyocyte maturation remain largely unexplored.
The lncRNA Cmarr promotes cardiomyocyte maturation and improves cardiac function post-myocardial infarction, highlighting its potential utility in cardiac patch therapies.
Hypothesis-generating for lncRNA-driven ESC-CM maturation; clinical translation of cardiac patches remains premature.
The immature phenotype of embryonic stem cell-derived cardiomyocytes (ESC-CMs) limits their application. However, the molecular mechanisms of cardiomyocyte maturation remain largely unexplored. This study found that overexpression of long noncoding RNA (lncRNA)-Cmarr, which was highly expressed in cardiomyocytes, promoted the maturation change and physiological maturation of mouse ESC-CMs (mESC-CMs). Moreover, transplantation of cardiac patch overexpressing Cmarr exhibited better retention of mESC-CMs, reduced infarct area by enhancing vascular density in the host heart, and improved cardiac function in mice after myocardial infarction. Mechanism studies identified that Cmarr acted as a competitive endogenous RNA to impede the repression of miR-540-3p on Dtna expression and promoted the binding of the dystrophin-glycoprotein complex (DGC) and yes-associated protein (YAP), which in turn reduced the proportion of nuclear YAP and the expression of YAP target genes. Therefore, this study revealed the function and mechanism of Cmarr in promoting cardiomyocyte maturation and provided a lncRNA that can be used as a functional factor in the construction of cardiac patches for the treatment of myocardial infarction.
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Wu et al. (2022) studied Myocardial Infarction (Preclinical model) (n=44). Cmarr-overexpressing mESC-CM cardiac patch vs. Control patch or MI alone was evaluated on Recovery of cardiac function (left-ventricular ejection fraction and fraction shortening) and infarct size. Transplantation of a cardiac patch overexpressing lncRNA Cmarr significantly reduced infarct size and improved cardiac function in a mouse model of myocardial infarction.
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