Effect of normal and PDK1-deficient human pluripotent stem cells on gene expression during cardiomyocytes differentiation.. Homo sapiens

Cardiac remodeling is the primary factor for the development of ischemic heart failure, which can result from various cardiomyopathies. Pyruvate Dehydrogenase Kinase1 (PDK1) is one of the components of AGC kinase family that maintain mitochondrial metabolism. We here report a PDK1-deficient human cardiac myocyte (CM) model that mimicked the human PDK1 homozygous frameshift mutation and determined the effects of PDK1 dysfunction and its underlying mechanism. PDK1 gene knockout did not affect the pluripotency and differentiation efficiency of hiPSCs. Myocardial cells with a PDK1 gene knockout showed abnormal metabolism, increased oxidative stress levels, decreased cell viability, and increased apoptosis. In addition, lentivirus transfection significantly improved the mitochondrial metabolism in the PDK1-deficient human myocardial model. Taken together, our data provide a PDK1-deficient human cardiomyocyte model that exhibits abnormal mitochondrial metabolism, this model represents an important tool to gain insight into the mechanism of action of metabolism disorders resulting in myocardial remodeling, elucidate the gene-phenotype relationship of PDK1 deficiency, and facilitate drug screening.