This study presents the following significant results: (1) knockdown of ZFAS1 protects cardiomyocytes against MI and hypoxia treatment-induced apoptosis; (2) upregulation of ZFAS1 expression induces cardiomyocyte apoptosis; (3) ZFAS1 induces cardiomyocyte apoptosis by inhibiting SERCA2a and causing cytosolic Ca2+ overload. The gene discussed is ZFAS1; the disease is myocardial infarction.