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

Bob S.L. Lee; Joshua K. Dunn; Cassandra Liang; Grace Chensee; Renhua Song; Cassandra Malecki; Elizabeth N. Robertson; Gavin J. Sutton; Christopher P. Stanley; Brett D. Hambly; Xiangjian Zheng; Paul G. Bannon; Wai Ho Tang; Justin J.L. Wong; Renjing Liu

doi:10.1016/j.jacbts.2025.101434

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

Bob S.L. Lee
, Joshua K. Dunn
, Cassandra Liang
, Grace Chensee
, Renhua Song
, Cassandra Malecki
, Elizabeth N. Robertson
, Gavin J. Sutton
, Christopher P. Stanley
, Brett D. Hambly
, Xiangjian Zheng
, Paul G. Bannon
, Wai Ho Tang
, Justin J.L. Wong
, Renjing Liu

Diagnostic Sciences

Research output: Contribution to journal › Article › peer-review

3 Citations (Scopus)

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^hi 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.

Original language	English
Article number	101434
Journal	JACC: Basic to Translational Science
Volume	11
Issue number	1
DOIs	https://doi.org/10.1016/j.jacbts.2025.101434
Publication status	Published - Jan 2026

UN SDGs

This output contributes to the following UN Sustainable Development Goals (SDGs)

SDG 3 Good Health and Well-being

Keywords

ascorbate
epigenetics
vascular calcification
vascular smooth muscle cells

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10.1016/j.jacbts.2025.101434

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Lee, B. S. L., Dunn, J. K., Liang, C., Chensee, G., Song, R., Malecki, C., Robertson, E. N., Sutton, G. J., Stanley, C. P., Hambly, B. D., Zheng, X., Bannon, P. G., Tang, W. H., Wong, J. J. L., & Liu, R. (2026). Epigenetic Reprogramming via TET2 Prevents Medial Calcification and Restores Vascular Smooth Muscle Cell Identity. JACC: Basic to Translational Science, 11(1), Article 101434. https://doi.org/10.1016/j.jacbts.2025.101434

@article{09f5440cceb74c3ea6e75cb2eed4e44d,

title = "Epigenetic Reprogramming via TET2 Prevents Medial Calcification and Restores Vascular Smooth Muscle Cell Identity",

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.",

keywords = "ascorbate, epigenetics, vascular calcification, vascular smooth muscle cells",

author = "Lee, \{Bob S.L.\} and Dunn, \{Joshua K.\} and Cassandra Liang and Grace Chensee and Renhua Song and Cassandra Malecki and Robertson, \{Elizabeth N.\} and Sutton, \{Gavin J.\} and Stanley, \{Christopher P.\} and Hambly, \{Brett D.\} and Xiangjian Zheng and Bannon, \{Paul G.\} and Tang, \{Wai Ho\} and Wong, \{Justin J.L.\} and Renjing Liu",

note = "Publisher Copyright: {\textcopyright} 2026 The Authors.",

year = "2026",

month = jan,

doi = "10.1016/j.jacbts.2025.101434",

language = "English",

volume = "11",

number = "1",

}

Lee, BSL, Dunn, JK, Liang, C, Chensee, G, Song, R, Malecki, C, Robertson, EN, Sutton, GJ, Stanley, CP, Hambly, BD, Zheng, X, Bannon, PG, Tang, WH, Wong, JJL & Liu, R 2026, 'Epigenetic Reprogramming via TET2 Prevents Medial Calcification and Restores Vascular Smooth Muscle Cell Identity', JACC: Basic to Translational Science, vol. 11, no. 1, 101434. https://doi.org/10.1016/j.jacbts.2025.101434

TY - JOUR

T1 - Epigenetic Reprogramming via TET2 Prevents Medial Calcification and Restores Vascular Smooth Muscle Cell Identity

AU - Lee, Bob S.L.

AU - Dunn, Joshua K.

AU - Liang, Cassandra

AU - Chensee, Grace

AU - Song, Renhua

AU - Malecki, Cassandra

AU - Robertson, Elizabeth N.

AU - Sutton, Gavin J.

AU - Stanley, Christopher P.

AU - Hambly, Brett D.

AU - Zheng, Xiangjian

AU - Bannon, Paul G.

AU - Tang, Wai Ho

AU - Wong, Justin J.L.

AU - Liu, Renjing

PY - 2026/1

Y1 - 2026/1

N2 - 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.

AB - 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.

KW - ascorbate

KW - epigenetics

KW - vascular calcification

KW - vascular smooth muscle cells

UR - https://www.scopus.com/pages/publications/105044360464

U2 - 10.1016/j.jacbts.2025.101434

DO - 10.1016/j.jacbts.2025.101434

M3 - Article

AN - SCOPUS:105044360464

SN - 2452-302X

VL - 11

JO - JACC: Basic to Translational Science

JF - JACC: Basic to Translational Science

IS - 1

M1 - 101434

ER -

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

Abstract

UN SDGs

Keywords

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