LncRNA-ZFAS1 Promotes Myocardial Ischemia-Reperfusion Injury Through DNA Methylation-Mediated Notch1 Down-Regulation in Mice

• The increase of ZFAS1 expression in MIRI is an important cause of cardiomyocyte apoptosis and ROS production. • ZFAS1 can directly interact with the promoter region of Notch1, recruit DNMT3b to promote DNA methylation in the promoter region of Notch1, and trigger cardiomyocyte apoptosis and ROS production after MIRI. • Nicotinamide mononucleotide has the potential to attenuate the apoptosis of cardiomyocytes after MIRI by competitively binding to DNMT3b and inhibiting the DNA methylation of Notch1. The most devastating and catastrophic deterioration of myocardial ischemia-reperfusion injury (MIRI) is cardiomyocyte death. Here we aimed to evaluate the role of lncRNA-ZFAS1 in MIRI and delineate its mechanism of action. The level of lncRNA-ZFAS1 was elevated in MIRI hearts, and artificial knockdown of lncRNA-ZFAS1 in mice improved cardiac function. Notch1 is a potential target of lncRNA-ZFAS1, and lncRNA-ZFAS1 could bind to the promoter region of Notch1 and recruit DNMT3b to induce Notch1 methylation. Nicotinamide mononucleotide could promote the expression of Notch1 by competitively inhibiting the expression of DNMT3b and improving the apoptosis of cardiomyocytes and cardiac function.