Associations of circulating T-cell subsets with carotid artery stiffness: the multiethnic study of atherosclerosis

Theodore M. DeConne, Petra Buzkova, Ryan Pewowaruk, Joseph A. Delaney, Bruce M. Psaty, Russell P. Tracy, Margaret F. Doyle, Colleen M. Sitlani, Alan L. Landay, Sally A. Huber, Timothy M. Hughes, Alain G. Bertoni, Adam D. Gepner, Jingzhong Ding, Nels C. Olson

Research output: Contribution to journalArticlepeer-review

Abstract

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, n = 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 (P-significance < 0.01) and 25 exploratory (P-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 CD4+CD28-CD57+, but not CD8+CD28-CD57+, T-cells were associated with higher LD-PWV (b = 0.04 m/s, P < 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.

Original languageEnglish (US)
Pages (from-to)H113-H119
JournalAmerican Journal of Physiology - Heart and Circulatory Physiology
Volume328
Issue number1
DOIs
StatePublished - Jan 2025
Externally publishedYes

Keywords

  • aging
  • arterial stiffness
  • epidemiology
  • risk factors
  • T-cells

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine
  • Physiology (medical)

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