Epigenetic Reprogramming via TET2 Prevents Medial Calcification and Restores Vascular Smooth Muscle Cell Identity

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 Trem2<sup>hi</sup> 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.

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Publication Details

Journal
JACC Basic to Translational Science
Published
2025-12-11
DOI
https://doi.org/10.1016/j.jacbts.2025.101434
Citations
1
Primary Topic
Epigenetics and DNA Methylation
Type
article
Field-Weighted Citation Impact
0.81
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article

Epigenetic Reprogramming via TET2 Prevents Medial Calcification and Restores Vascular Smooth Muscle Cell Identity

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JACC Basic to Translational Science
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article

Epigenetic Reprogramming via TET2 Prevents Medial Calcification and Restores Vascular Smooth Muscle Cell Identity

Wai Ho Tang, Cassandra Malecki, Grace Chensee, Bob S. L. Lee, Gavin J Sutton, Christopher P. Stanley, Paul G. Bannon, Renhua Song, E. Robertson, Cassandra Liang, Brett D. Hambly, Renjing Liu, Xiangjian Zheng, J DUNN, Justin Wong
article en
1 citations

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 Trem2<sup>hi</sup> 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.

JACC Basic to Translational ScienceVol. 11(1)
The University of Sydney (AU), Victor Chang Cardiac Research Institute (AU), Royal Prince Alfred Hospital (AU), The Heart Research Institute (AU), Sydney Hospital (AU), Guangzhou Women and Children Medical Center (CN), Baird Institute (AU), Tianjin Medical University (CN), Guangzhou Medical University (CN)
Openalex Percentile: Top 21%
Epigenetics and DNA Methylation
0.81
DOIOpen Access PDFOpenAlex
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