Cardiovascular research · 2025
Senescent CD8+ T cells: a novel risk factor in atrial fibrillation.
СтатьяНазвание и аннотация: Перевод в очереди
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Li Xiang, Bao Yangyang, Zhang Ning, Lin Changjian, Xie Yun, Wei Yue, Luo Qingzhi, Liu Jingmeng, Sha Zimo, Wu Guanhua, Zhou Taojie, Chen Qiujing, Ling Tianyou, Pan Wenqi, Lu Lin, Wu Liqun, Dai Yang, Jin Qi
Аннотация
AIMS: Immune cell alterations may play a role in the development of atrial fibrillation (AF). Our objective was to comprehensively characterize immune cells in AF, and investigate the potential mechanisms.
METHODS AND RESULTS: Single-cell RNA sequencing and multicolour flow cytometry revealed that T cells constituted the most significant subset alterations in AF, and senescent CD8+ T cells were AF-associated subset. Senescent CD8+ T cells increased in both peripheral veins (P < 0.0001) and the left atria (P < 0.05) in patients with AF compared to non-AF control. Senescent CD8+ T cells were independently associated with AF prevalence (odds ratio = 2.876, P < 0.05) and postprocedural recurrence (hazard ratio = 22.955, P < 0.0001) using a cross-sectional study and a subsequent prospective cohort study. Senescent CD8+ T cells secreted an increased amount of interferon (IFN)-γ, which induces Ca2+ handling abnormalities in human induced pluripotent stem cell-derived atrial cardiomyocytes, and translated into an increased susceptibility to AF assessed by heart optical mapping.
CONCLUSIONS: An increased amount of senescent CD8+ T cells may be a hallmark of the immune senescence phenotype in AF and potentially serve as a valid biomarker for assessing prevalence and postprocedural recurrence of AF. By connecting immune senescence with electrophysiological disturbances in AF, this research provides a potential mechanism for the involvement of senescent CD8+ T cells in proarrhythmic calcium disorders and suggests novel avenues for developing new immune-modulatory and senolytic therapies for AF.
METHODS AND RESULTS: Single-cell RNA sequencing and multicolour flow cytometry revealed that T cells constituted the most significant subset alterations in AF, and senescent CD8+ T cells were AF-associated subset. Senescent CD8+ T cells increased in both peripheral veins (P < 0.0001) and the left atria (P < 0.05) in patients with AF compared to non-AF control. Senescent CD8+ T cells were independently associated with AF prevalence (odds ratio = 2.876, P < 0.05) and postprocedural recurrence (hazard ratio = 22.955, P < 0.0001) using a cross-sectional study and a subsequent prospective cohort study. Senescent CD8+ T cells secreted an increased amount of interferon (IFN)-γ, which induces Ca2+ handling abnormalities in human induced pluripotent stem cell-derived atrial cardiomyocytes, and translated into an increased susceptibility to AF assessed by heart optical mapping.
CONCLUSIONS: An increased amount of senescent CD8+ T cells may be a hallmark of the immune senescence phenotype in AF and potentially serve as a valid biomarker for assessing prevalence and postprocedural recurrence of AF. By connecting immune senescence with electrophysiological disturbances in AF, this research provides a potential mechanism for the involvement of senescent CD8+ T cells in proarrhythmic calcium disorders and suggests novel avenues for developing new immune-modulatory and senolytic therapies for AF.
Предметные рубрики MeSH
HumansAtrial FibrillationCD8-Positive T-LymphocytesCellular SenescenceMaleRisk FactorsFemaleCross-Sectional StudiesMiddle AgedAgedProspective StudiesMyocytes, CardiacInterferon-gammaCase-Control StudiesRisk AssessmentPhenotypeCalcium SignalingCells, CulturedHeart RateImmunosenescenceRecurrenceSingle-Cell Analysis