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Volume 6 Issue 2
Apr.  2026
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Article Navigation >  Frigid Zone Medicine  > 2026  >  6(2): 86-96
Hui Yu, Longfei Hao, Rui Wang, Yongtai Gong, Yue Li. TIE1 is a potential target for hypertension-related atrial fibrillation[J]. Frigid Zone Medicine, 2026, 6(2): 86-96. doi: 10.1515/fzm-2026-0009
Citation: Hui Yu, Longfei Hao, Rui Wang, Yongtai Gong, Yue Li. TIE1 is a potential target for hypertension-related atrial fibrillation[J]. Frigid Zone Medicine, 2026, 6(2): 86-96. doi: 10.1515/fzm-2026-0009
shu

TIE1 is a potential target for hypertension-related atrial fibrillation

doi: 10.1515/fzm-2026-0009
  • 1.

    Department of Cardiology, The First Affiliated Hospital, Harbin Medical University, Harbin 150001, China

  • 2.

    Key Laboratory of Cardiac Diseases and Heart Failure, Harbin Medical University, Harbin 150001, China

  • 3.

    State Key Laboratory of Frigid Zone Cardiovascular Disease, Harbin Medical University, Harbin 150086, China

Funds:

the Key Research and Development Plan of Heilongjiang Province to Li Y 2022ZX06C23

the Key Research and Development Plan of Heilongjiang Province to Li Y JD2023SJ44

More Information
  • Corresponding author: Yongtai Gong, E-mail: gongth@126.com; Yue Li, E-mail: ly99ly@hrbmu.edu.cn
  • Received Date: 2025-08-24
  • Accepted Date: 2025-09-07
    • Available Online: 2026-04-01
    Abstract
  •   Objective  Cardiovascular diseases pose a major public health challenge in China, particularly in northern frigid regions where environmental stressors and limited access to healthcare access exacerbate disease risk. Both atrial fibrillation (AF) and hypertension are influenced by cold exposure. AF is a frequent cardiovascular complication of hypertension, yet their causal relationship remains incompletely defined. This study aimed to elucidate the mechanisms linking hypertension to AF in frigid regions, with an emphasis on identifying key genes driving disease progression.  Methods  We analyzed clinical data from 29,786 patients hospitalized at the First Affiliated Hospital of Harbin Medical University. Multivariate logistic regression was used to assess the association between hypertension and AF, and Mendelian randomization (MR) analyses were performed using genome-wide association study (GWAS) datasets. Whole-blood expression quantitative trait locus (eQTL) analysis and pathway enrichment were applied to identify hypertension-related genes. Single-cell RNA sequencing data from AF patients and hypertensive rat models were used to validate the role of TIE1. In addition, gut microbiota GWAS data were integrated to explore microbial influences on hypertension.  Results  Hypertension emerged as both an independent and causal risk factor for AF in frigid regions. Gene expression analyses identified TIE1 as a central mediator of hypertension-related effects, with elevated cardiomyocyte TIE1 expression associated with increased susceptibility to AF. In hypertensive rats, increased TIE1 expression correlated with higher AF incidence and enhanced inflammatory cytokine production, whereas cardiomyocyte-specific TIE1 knockdown reduced AF occurrence and attenuated atrial remodeling. Gut microbiota analysis further revealed that the abundance of Adlercreutzia was inversely correlated with TIE1 expression, suggesting a potential protective role mediated through microbial regulation of host gene expression.  Conclusion  These findings establish a causal link between hypertension and AF in cold northern regions and identify TIE1 as a pivotal mediator of this association. Targeting TIE1 may represent a therapeutic strategy for hypertension-associated AF. Moreover, the identification of Adlercreutzia as a modulator of TIE1 underscores the potential of the gut microbiota in preventing cardiovascular complications in frigid regions and opens promising avenues for future interventions.

     

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