Potential Compensatory Role of Ten-Eleven Translocation (TET)3 in Vascular Smooth Muscle Cell Plasticity

Authors: Melinee D’Silva, Comfort Williams and Sachin A. Gupte

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This poster presentation, co-authored by Melinee D'Silva and colleagues, explores the role of Ten-Eleven Translocation (TET) enzymes—specifically investigating a potential compensatory role for TET3—in vascular smooth muscle cell (VSMC) plasticity during atherosclerosis. The study examines phenotypic switching, where human coronary artery smooth muscle cells (hCASMCs) shift from a healthy contractile state to a disease-promoting inflammatory state. Utilizing the pharmacological inhibitor Bobcat339 to block TET1 and TET2 activity, the researchers observed changes in DNA demethylation pathways (the conversion of 5mc to 5hmc), which led to a downregulation of contractile marker genes (such as MYOCCD and MYH11) and an upregulation of inflammatory signaling. The results highlight how TET-mediated epigenetic regulation controls this phenotypic transition, concluding that targeting these pathways could offer therapeutic avenues.

Future directions focus on genetic and pharmacological approaches to reverse atherosclerotic smooth muscle remodeling, including collaboration with the University of Buffalo to develop novel TET activators.