DeConne Theodore M, Buzkova Petra, Pewowaruk Ryan, Delaney Joseph A, Psaty Bruce M, Tracy Russell P, Doyle Margaret F, Sitlani Colleen M, Landay Alan L, Huber Sally A, Hughes Timothy M, Bertoni Alain G, Gepner Adam D, Ding Jingzhong, Olson Nels C
Section of Gerontology and Geriatric Medicine, Department of Internal Medicine, Wake Forest University School of Medicine, Winston-Salem, North Carolina, United States.
Department of Biostatistics, University of Washington, Seattle, Washington, United States.
Am J Physiol Heart Circ Physiol. 2025 Jan 1;328(1):H113-H119. doi: 10.1152/ajpheart.00649.2024. Epub 2024 Nov 26.
Arterial stiffness measured by total pulse wave velocity (T-PWV) is associated with an increased risk of multiple age-related diseases. T-PWV can be described by structural (S-PWV) and load-dependent (LD-PWV) arterial stiffening. T-cells have been implicated in arterial remodeling, arterial stiffness, and hypertension in humans and animals; however, it is unknown whether T-cells are risk factors for T-PWV or its components. Therefore, we evaluated the cross-sectional associations of peripheral T-cell subpopulations with T-PWV, S-PWV, and LD-PWV. Peripheral blood T-cells were characterized using flow cytometry, and carotid artery stiffness was measured using B-mode ultrasound to calculate T-PWV at the baseline examination in a participant subset of the Multi-Ethnic Study of Atherosclerosis (MESA, = 1,984). A participant-specific exponential model was used to calculate S-PWV and LD-PWV based on elastic modulus and blood pressure gradients. The associations between five primary (-significance < 0.01) and 25 exploratory (-significance < 0.05) immune cell subpopulations, per 1-SD increment, and arterial stiffness measures were assessed using adjusted linear regression models. For the primary analysis, higher CD4CD28CD57, but not CD8CD28CD57, T-cells were associated with higher LD-PWV (β = 0.04 m/s, < 0.01) after adjusting for covariates. None of the remaining T-cell subpopulations in the primary analysis were associated with T-PWV or S-PWV. For the exploratory analysis, several memory and differentiated/senescence-associated CD4 and CD8 T-cell subpopulations were associated with greater T-PWV, S-PWV, and LD-PWV after adjusting for covariates. In conclusion, we highlight novel associations in humans between CD4 and CD8 memory and differentiated/senescence-associated T-cell subpopulations and measures of arterial stiffness in MESA. These results warrant longitudinal, prospective studies that examine changes in T-cell subpopulations and arterial stiffness in humans. We investigated associations between T-cells and novel measures of structural and load-dependent arterial stiffness in a large multiethnic cohort. The primary analysis revealed that pro-inflammatory, senescence-associated CD4CD28CD57 T-cells were associated with higher load-dependent arterial stiffness. An exploratory analysis revealed that multiple pro-inflammatory CD4 and CD8 T-cell subpopulations were associated with both higher structural and load-dependent arterial stiffness. These results suggest that pro-inflammatory T-cells may contribute to arterial stiffness through both arterial remodeling and elevated blood pressure.
通过总脉搏波速度（T-PWV）测量的动脉僵硬度与多种年龄相关疾病风险增加有关。T-PWV可由结构性（S-PWV）和负荷依赖性（LD-PWV）动脉僵硬度来描述。在人类和动物中，T细胞与动脉重塑、动脉僵硬度和高血压有关；然而，尚不清楚T细胞是否是T-PWV或其组成部分的危险因素。因此，我们评估了外周血T细胞亚群与T-PWV、S-PWV和LD-PWV之间的横断面关联。在动脉粥样硬化多族裔研究（MESA，n = 1984）的一个参与者子集中，在基线检查时使用流式细胞术对外周血T细胞进行表征，并使用B型超声测量颈动脉僵硬度以计算T-PWV。基于弹性模量和血压梯度，使用参与者特异性指数模型计算S-PWV和LD-PWV。使用调整后的线性回归模型评估每1-SD增量的五个主要（P值<0.01）和25个探索性（P值<0.05）免疫细胞亚群与动脉僵硬度测量值之间的关联。在进行主要分析时，在调整协变量后，较高的CD4CD28CD57而非CD8CD28CD57 T细胞与较高的LD-PWV相关（β = 0.04 m/s，P<0.01）。主要分析中其余的T细胞亚群均与T-PWV或S-PWV无关。在进行探索性分析时，在调整协变量后，几个记忆性和分化/衰老相关的CD4和CD8 T细胞亚群与更高的T-PWV、S-PWV和LD-PWV相关。总之，我们在MESA研究中突出了人类CD4和CD8记忆性以及分化/衰老相关T细胞亚群与动脉僵硬度测量值之间的新关联。这些结果需要进行纵向前瞻性研究，以检查人类T细胞亚群和动脉僵硬度的变化。我们在一个大型多族裔队列中研究了T细胞与结构性和负荷依赖性动脉僵硬度新测量指标之间的关联。主要分析显示，促炎、衰老相关的CD4CD28CD57 T细胞与较高的负荷依赖性动脉僵硬度相关。探索性分析显示，多个促炎CD4和CD8 T细胞亚群与较高的结构性和负荷依赖性动脉僵硬度均相关。这些结果表明促炎T细胞可能通过动脉重塑和血压升高导致动脉僵硬度增加。
