Code from: Metabolic control of smooth muscle cell phenotype switching in atherosclerosis

However, its metabolic basis is not entirely elucidated. Since transforming growth factor beta (TGFβ) signaling is among the principal regulators of SMC contractility, we studied the metabolic regulation of TGFβ signaling in SMCs in vitro and atherosclerotic mouse models and human lesions.

We found that TGFβ induced Ac-CoA synthetase 2 (ACSS2)-dependent Ac-CoA production by suppressing pyruvate dehydrogenase kinase 4 (PDK4). This stabilized R-SMADs and TGFβ receptor 1, preserving SMC contractile phenotype. SMC-specific PDK4 knockout mimicked the effect of TGFβ signaling both metabolically and phenotypically, increasing glucose-derived synthesis of Ac-CoA and SMC contractile phenotype.