Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques, levels of LDL, and cardiorespiratory fitness in the elderly

Tim Böttrich; Pascal Bauer; Vincent Gröβer; Magdalena Huber; Hartmann Raifer; Torsten Frech; Svenja Nolte; Theresa Dombrowski; Franz Cemic; Natascha Sommer; Robert Ringseis; Klaus Eder; Karsten Krüger; Christopher Weyh

doi:10.1016/j.jshs.2023.11.004

Subpopulations of regulatory T cells are associated with subclinical atherosclerotic plaques, levels of LDL, and cardiorespiratory fitness in the elderly

J Sport Health Sci. 2023 Nov 10:S2095-2546(23)00113-8. doi: 10.1016/j.jshs.2023.11.004. Online ahead of print.

Authors

Affiliations

¹ Department of Exercise Physiology and Sports Therapy, Institute of Sports Science, Justus-Liebig-University, Giessen 35394, Germany.
² Department of Cardiology and Angiology, Justus-Liebig-University Giessen, Giessen 35392, Germany.
³ Institute for Systems Immunology, Center for Tumor und Immunology, Marburg 35032, Germany.
⁴ TH Mittelhessen, Department of Computer Science, University of Applied Sciences Giessen, Giessen 35390, Germany.
⁵ Department of Internal Medicine, Universities of Giessen and Marburg Lung Center (UGMLC), Member of the German Center for Lung Research (DZL), Excellence Cluster Cardio-Pulmonary Institute (CPI), Justus-Liebig University, Giessen 35394, Germany.
⁶ Institute of Animal Nutrition and Nutrition Physiology, Justus-Liebig-University Giessen, Giessen 35390, Germany.
⁷ Department of Exercise Physiology and Sports Therapy, Institute of Sports Science, Justus-Liebig-University, Giessen 35394, Germany. Electronic address: karsten.krueger@sport.uni-giessen.de.

PMID: 37951470
DOI: 10.1016/j.jshs.2023.11.004

Abstract

Background: Atherosclerosis forms the pathological basis for the development of cardiovascular disease. Since pathological processes initially develop without clinically relevant symptoms, the identification of early markers in the subclinical stage plays an important role for initiating early interventions. There is evidence that regulatory T cells (T_regs) are involved in the development of atherosclerosis. Therefore, the present study aimed to identify and investigate associations with T_regs and their subsets in a cohort of healthy elderly individuals with and without subclinical atherosclerotic plaques (SAP). In addition, various lifestyle and risk factors, such as cardiorespiratory fitness, were investigated as associated signatures.

Methods: A cross-sectional study was performed in 79 participants (male: n = 50; age = 63.6 ± 3.7 years; body mass index = 24.9 ± 3.1 kg/m²; mean ± SD) who had no previous diagnosis of chronic disease and were not taking medication. Ultrasound of the carotids to identify SAP, cardiovascular function measurement for vascular assessment and a cardiorespiratory fitness test to determine peak oxygen uptake were performed. Additionally, tests were conducted to assess blood lipids and determine glucose levels. Immunophenotyping of T_regs and their subtypes (resting (rT_regs) and effector/memory (mT_regs)) was performed by 8-chanel flow cytometry. Participants were categorized according to atherosclerotic plaque status. Linear and logistic regression models were used to analyze associations between parameters.

Results: SAP was detected in a total of 29 participants. The participants with plaque were older (64.5 ± 3.6 years vs. 62.9 ± 3.5 years) and had higher peripheral systolic blood pressure (133.8 ± 14.7 mmHg vs. 125.8 ± 10.9 mmHg). The participants with SAP were characterized by a lower percentage of rT_regs (28.8% ± 10.7% vs. 34.6% ± 10.7%) and a higher percentage of mT_regs (40.3% ± 14.7% vs. 30.0% ± 11.9%). Multiple logistic regression identified age (odds ratio (OR) = 1.20 (95% confidence interval (95%CI): 1.01-1.42)) and mT_regs (OR = 1.05 (95%CI: 1.02-1.10)) as independent risk factors for SAP. Stepwise linear regression could reveal an association of peak oxygen uptake (β = 0.441), low-density lipoprotein (LDL) (β = -0.096), and SAP (β = 6.733) with mT_regs and LDL (β = 0.104) with rT_regs.

Conclusion: While at an early stage of SAP, the total proportion of T_regs gives no indication of vascular changes, this is indicated by a shift in the T_reg subgroups. Factors such as serum LDL or cardiopulmonary fitness may be associated with this shift and may also be additional diagnostic indicators. This could be used to initiate lifestyle-based preventive measures at an early stage, which may have a protective effect against disease progression.

Keywords: Cardiorespiratory fitness; Elderly; Regulatory T cells; Subclinical atherosclerosis.