2. Academic Validation
  3. Telomere Shortening Drives Atrial Fibrillation Through VCAM-1 Mediated Atrial Electrical and Structural Remodeling

Telomere Shortening Drives Atrial Fibrillation Through VCAM-1 Mediated Atrial Electrical and Structural Remodeling

  • Aging Cell. 2026 Feb;25(2):e70417. doi: 10.1111/acel.70417.
Zhaojia Wang 1,  Rui Zhao 2,  Yuwen Wang 2,  Nan Zhang 1,  Qiuhui Yang 2,  Zandong Zhou 1,  Duo Jiang 2,  Xu Zhang 1,  Jinghua Yuan 2 3,  Yi Zheng 1,  Wenhua Song 1,  Daiqi Liu 1,  Xunzhi Liu 4,  Kejing Yuan 4,  Gary Tse 1 5,  Gregory Y H Lip 1 6 7 8,  Tong Liu 1,  Feng Wang 2 9
Affiliations

Affiliations

  • 1 Tianjin Key Laboratory of Ion and Molecular Function of Cardiovascular Diseases, Department of Cardiology, Second Hospital of Tianjin Medical University, Tianjin Institute of Cardiology, Tianjin, China.
  • 2 Department of Genetics, School of Basic Medical Science, Tianjin Medical University, The Province and Ministry Co-Sponsored Collaborative Innovation Center for Medical Epigenetics, Tianjin, People's Republic of China.
  • 3 Key Laboratory of Artificial Organs and Computational Medicine in Zhejiang Province, Shulan International Medical College, Zhejiang Shuren University, Hangzhou, People's Republic of China.
  • 4 Shanghai Fuyang Biotechnology Co., LTD, Shanghai, China.
  • 5 School of Nursing and Health Sciences, Hong Kong Metropolitan University, Hong Kong, China.
  • 6 Liverpool Centre for Cardiovascular Science at University of Liverpool, Liverpool John Moores University and Liverpool Heart & Chest Hospital, Liverpool, UK.
  • 7 Department of Clinical Medicine, Aalborg University, Aalborg, Denmark.
  • 8 Medical University of Bialystok, Bialystok, Poland.
  • 9 Tianjin Key Laboratory of Cellular and Molecular Immunology, Tianjin, People's Republic of China.
PMID: 41685883 DOI: 10.1111/acel.70417
Abstract

Telomere shortening is a hallmark of aging and has been implicated in Cardiovascular Disease, but its mechanistic link to atrial fibrillation (AF) remains elusive. Using a high-throughput, single-gene-calibrated dot blot assay, we developed to quantify leukocyte telomere length (LTL). In age-stratified analyses, shorter LTL was associated with AF predominantly in individuals younger than 70 years. In telomerase-deficient (TERT-/-) mice with telomere dysfunction, higher AF inducibility, atrial electrical conduction slowing, and atrial fibrosis were observed. Transcriptomic profiling revealed significant alterations in extracellular matrix and cell adhesion pathways in response to telomere dysfunction. Subsequent validation identified vascular cell adhesion molecule-1 (VCAM-1) as a potential mediator linking telomere shortening to AF-related atrial remodeling. Functional inhibition of VCAM-1 reversed electrophysiological abnormalities, attenuated atrial fibrosis, normalized ECM gene expression-including Col1α1, α-SMA, and CD168-and reduced AF susceptibility by 30%. These findings establish a telomere-VCAM-1 axis that drives atrial remodeling and arrhythmogenesis in aging, and position VCAM-1 as a candidate therapeutic target for age-related AF.

Keywords

TERT; VCAM‐1; aging; atrial fibrillation; telomere.

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