Epigenetic Reprogramming via TET2 Prevents Medial Calcification and Restores Vascular Smooth Muscle Cell Identity
Year: 2025
Type: article
Abstract: Vascular calcification arises from the osteogenic transdifferentiation of vascular smooth muscle cells (VSMCs) and is a hallmark of many cardiovascular pathologies. This study identifies Tet2, a DNA demethylase, as a critical epigenetic regulator that prevents this phenotypic switch. VSMC-specific loss of Tet2 promotes osteogenic differentiation, apoptosis, increased infiltration of Trem2hi macrophages and medial aortic calcification. High-dose ascorbate used to enhance Tet2 activity significantly reduced calcification and preserved aortic structure in mice. These findings support Tet2 reactivation as a potential therapeutic strategy to prevent or reverse vascular calcification in cardiovascular disease.
Institutions: Victor Chang Cardiac Research Institute, UNSW Sydney, The University of Sydney, The Heart Research Institute, Tianjin Medical University, Royal Prince Alfred Hospital, Baird Institute, Guangzhou Women and Children Medical Center, Hong Kong Metropolitan University, Guangzhou Medical University
Language: English
Subfield: Genetics
Domain: Life Sciences
Open Access status: gold
Estimated APC paid: $4,750
OpenAlex ID: W4417304299