HDAC Expression and Activity in Vascular Smooth Muscle Cells is Regulated by Glucose‐6‐Phosphate Dehydrogenase

Glucose‐6‐phosphate dehydrogenase (G6PD), a key enzyme in the glucose metabolism, regulates vascular smooth muscle cell (VSMC) phenotype and function. In proteomic analysis, we discovered that G6PD formed a complex with histone acyltransferase (KAT6A) and deacetylase (HDAC5) in VSMCs. Therefore, we investigated whether HDAC expression and activity is regulated by G6PD in pulmonary artery and aortic smooth muscle cells. G6PD knock down decreased HDAC5 expression and G6PD inhibition decreased HDAC activity by 70‐80%. G6PD inhibition also decreased cell proliferation and increased myocardin and myocardin‐dependent gene expression. In summary, we propose that: 1) G6PD‐dependent HDAC function is involved in the regulation of VSMC‐specific genes and VSMC phenotype, and 2) G6PD‐dependent HDAC activation could be important in down‐regulating myocardin gene expression and activity and in switching smooth muscle cell phenotype that mediates remodeling of arteries in diseases like pulmonary hypertension and metabolic syndrome.