Abstract：
BACKGROUND: Abnormal immune responses, particularly T-cell activity, are linked to vascular complications in hypertension, but mechanisms remain unknown. Our study aims to explore the association between arterial stiffness, assessed by brachial-ankle pulse wave velocity (baPWV), and T-cell receptor (TCR) repertoires in essential hypertension patients, focusing on understanding the role of T cells in the development of arterial stiffness in this population.
METHODS: The study included 301 essential hypertension patients and 48 age-matched normotensive controls. Essential hypertension patients were stratified into high (baPWV ≥1400 cm/s, n = 213) and low (baPWV <1400 cm/s, n = 88) baPWV groups. High-throughput sequencing analyzed peripheral TCRβ repertoires.
RESULTS: Significant TCRβ repertoire differences were observed between essential hypertension and normotensive groups, as well as between high and low baPWV essential hypertension subgroups. Specifically, patients in the high baPWV group exhibited notable variations in the utilization of specific TCR beta joining (TRBJ) and variable (TRBV) genes compared to the low baPWV group. These alterations were accompanied by reduced TCRβ diversity (represented by diversity 50 s), increased percentages of the largest TCRβ clones, and a higher number of TCRβ clones exceeding 0.1%. The presence of specific TCRβ clones was detected in both groups. Furthermore, reduced diversity 50s and elevated percentages of the largest TCRβ clones were independently correlated with baPWV, emerging as potential risk factors for increased baPWV in essential hypertension patients.
CONCLUSIONS: TCR repertoires were independently associated with arterial stiffness in patients with essential hypertension, implicating a potential role for dysregulated T-cell responses in the pathogenesis of arterial stiffness in this patient population.Trial registration: ChiCTR2100054414.
METHODS: The study included 301 essential hypertension patients and 48 age-matched normotensive controls. Essential hypertension patients were stratified into high (baPWV ≥1400 cm/s, n = 213) and low (baPWV <1400 cm/s, n = 88) baPWV groups. High-throughput sequencing analyzed peripheral TCRβ repertoires.
RESULTS: Significant TCRβ repertoire differences were observed between essential hypertension and normotensive groups, as well as between high and low baPWV essential hypertension subgroups. Specifically, patients in the high baPWV group exhibited notable variations in the utilization of specific TCR beta joining (TRBJ) and variable (TRBV) genes compared to the low baPWV group. These alterations were accompanied by reduced TCRβ diversity (represented by diversity 50 s), increased percentages of the largest TCRβ clones, and a higher number of TCRβ clones exceeding 0.1%. The presence of specific TCRβ clones was detected in both groups. Furthermore, reduced diversity 50s and elevated percentages of the largest TCRβ clones were independently correlated with baPWV, emerging as potential risk factors for increased baPWV in essential hypertension patients.
CONCLUSIONS: TCR repertoires were independently associated with arterial stiffness in patients with essential hypertension, implicating a potential role for dysregulated T-cell responses in the pathogenesis of arterial stiffness in this patient population.Trial registration: ChiCTR2100054414.
摘要：
背景：异常免疫反应，特别是T细胞活性，与高血压的血管并发症有关，但机制仍然未知。我们的研究旨在探讨动脉僵硬度之间的关系，通过臂踝脉搏波速度（baPWV）评估，和原发性高血压患者的T细胞受体（TCR）库，重点了解T细胞在该人群动脉僵硬发展中的作用。
方法：该研究包括301例原发性高血压患者和48例年龄匹配的正常血压对照。原发性高血压患者分层为高（baPWV≥1400cm/s，n=213）和低（baPWV<1400cm/s，n=88)baPWV组。高通量测序分析了外周TCRβ库。
结果：在原发性高血压组和正常血压组之间观察到了显著的TCRβ谱差异，以及高和低baPWV原发性高血压亚组之间。具体来说,与低baPWV组相比,高baPWV组患者在特异性TCRβ连接(TRBJ)和可变(TRBV)基因利用方面表现出显著差异.这些改变伴随着减少的TCRβ多样性(以多样性50秒表示)，最大的TCRβ克隆的百分比增加，和超过0.1%的较高数量的TCRβ克隆。在两组中均检测到特异性TCRβ克隆的存在。此外，最大TCRβ克隆的多样性降低50s和百分比升高与baPWV独立相关，成为原发性高血压患者baPWV升高的潜在危险因素。
结论：TCR谱与原发性高血压患者的动脉僵硬度独立相关，提示T细胞反应失调在该患者人群动脉僵硬的发病机理中的潜在作用。试用注册:ChiCTR2100054414。
方法：该研究包括301例原发性高血压患者和48例年龄匹配的正常血压对照。原发性高血压患者分层为高（baPWV≥1400cm/s，n=213）和低（baPWV<1400cm/s，n=88)baPWV组。高通量测序分析了外周TCRβ库。
结果：在原发性高血压组和正常血压组之间观察到了显著的TCRβ谱差异，以及高和低baPWV原发性高血压亚组之间。具体来说,与低baPWV组相比,高baPWV组患者在特异性TCRβ连接(TRBJ)和可变(TRBV)基因利用方面表现出显著差异.这些改变伴随着减少的TCRβ多样性(以多样性50秒表示)，最大的TCRβ克隆的百分比增加，和超过0.1%的较高数量的TCRβ克隆。在两组中均检测到特异性TCRβ克隆的存在。此外，最大TCRβ克隆的多样性降低50s和百分比升高与baPWV独立相关，成为原发性高血压患者baPWV升高的潜在危险因素。
结论：TCR谱与原发性高血压患者的动脉僵硬度独立相关，提示T细胞反应失调在该患者人群动脉僵硬的发病机理中的潜在作用。试用注册:ChiCTR2100054414。
