Reduced Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients With Essential Hypertension and Subclinical Carotid Atherosclerosis

Xiaoxiang Ma; Yue Zhuo; Yu Huang; Pengming He; Zhaoyi Huang; Li Jiang; Luyao Tong; Xiaoqin Yao; Xueping Wen; Xuemei Zhong; Shihan Yang; Changqiong Li; Yuping Liu; Zhixin Zhang

doi:10.1161/HYPERTENSIONAHA.123.21112

Reduced Diversities and Clonally Expanded Sequences of T-Cell Receptors in Patients With Essential Hypertension and Subclinical Carotid Atherosclerosis

Hypertension. 2023 Nov;80(11):2318-2329. doi: 10.1161/HYPERTENSIONAHA.123.21112. Epub 2023 Aug 8.

Authors

Xiaoxiang Ma^#¹, Yue Zhuo^#¹, Yu Huang¹, Pengming He², Zhaoyi Huang¹, Li Jiang¹, Luyao Tong¹, Xiaoqin Yao¹, Xueping Wen², Xuemei Zhong², Shihan Yang², Changqiong Li², Yuping Liu¹, Zhixin Zhang¹

Affiliations

¹ Department of Health Management & Institute of Health Management, Sichuan Provincial People's Hospital, University of Electronic Science and Technology of China, Chengdu, Sichuan (X.M., Y.Z., Y.H., Z.H., L.J., L.T., X.Y., Y.L., Z.Z.).
² Chengdu ExAb Biotechnology LTD, Chengdu, Sichuan, China (P.H., X.W., X.Z., S.Y., C.L.).

^# Contributed equally.

PMID: 37551594
DOI: 10.1161/HYPERTENSIONAHA.123.21112

Abstract

Background: It has long been hypothesized that the abnormal immune responses contribute to the essential hypertension (EH) and its subclinical target organ damage (STOD). However, the mechanism is unclear. This study aimed at exploring the potential association with abnormal T-cell responses and EH, STOD, and early atherosclerosis in patients with EH.

Methods: This cross-sectional study included 146 patients with EH and 73 age-matched normotensive individuals. The expressed peripheral TCR (T-cell receptor) β repertoire was analyzed by high through-put sequencing.

Results: The TCRβ repertoires of the patients with EH were significantly different, with significantly elevated certain TCR beta variable (TRBV) and joint (TRBJ) gene usages, significantly reduced TCRβ diversity indexes (diversity 50s) and numbers of total TCRβ clonal types, significantly elevated percentages of the biggest TCRβ clones and numbers of clones accounting >0.1% sequences, compared with those in the normotensive controls. Decreased diversity 50s and increased biggest TCRβ clone percentages were independently correlated with carotid intima-media thickness and subclinical carotid atherosclerosis (SCA) in the patients with EH. Moreover, the diversity 50s were further significantly reduced and the biggest TCRβ clone percentages were significantly increased in the patients with EH with SCA (n=89) comparing to the patients with EH/patients without SCA (n=57), and in patients with EH/SCA with carotid plaque (n=22) comparing to patients with EH/SCA/patients without carotid plaque (n=67). Importantly, specific TCRβ clones were identified in different subgroups of the patients with EH.

Conclusions: These results reveal that abnormal T-cell responses may play important roles in the progression of EH and its SCA, especially the formation of carotid plaque.

Registration: URL: https://www.chictr.org.cn; Unique identifier: ChiCTR2100054414.

Keywords: atherosclerosis; blood pressure; cardiovascular diseases; carotid intima-media thickness; essential hypertension.

MeSH terms

Carotid Artery Diseases*
Carotid Intima-Media Thickness*
Cross-Sectional Studies
Essential Hypertension
Humans
Receptors, Antigen, T-Cell
Risk Factors

Substances

Receptors, Antigen, T-Cell

Associated data

ClinicalTrials.gov/ChiCTR2100054414