Early life thymectomy induces arterial dysfunction in mice

Buckley, David J.; Sharma, Sunita; Joseph, Blessy; Fayyaz, Alia H.; Canizales, Alexandra; Terrebonne, Konner J.; Trott, Daniel W.

doi:10.1007/s11357-023-00853-y

Cited by 2 publications

(1 citation statement)

References 59 publications

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“…Adaptive T-lymphocytes (T-cells) have been associated with arterial stiffness and its associated components (e.g., arterial remodeling and blood pressure) [11][12][13][14][15][16][17] . For example, CD4 + CD45RA + T-cells were associated with lower common carotid artery intima-media thickness (CCA IMT) and higher proportions CD4 + CD45RO + (memory) T-cells and pro-inflammatory CD4 + IFN-γ + (Th1) T-cells were associated with greater CCA IMT in the Multi-Ethnic Study of Atherosclerosis (MESA) 11,17 .…”

Section: Introductionmentioning

confidence: 99%

Associations of circulating T-cell subsets in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis

DeConne,

Buzkova,

Pewowaruk

et al. 2024

Preprint

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Background: Arterial stiffness measured by total pulse wave velocity (T-PWV) is associated with 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 associated with arterial remodeling, blood pressure, and arterial stiffness in humans and animals; however, it is unknown whether T-cells are related to S-PWV or LD-PWV. Therefore, we evaluated the cross-sectional associations of peripheral T-cell subpopulations with T-PWV, S-PWV, and LD-PWV stiffness. Methods: Peripheral blood T-cells were characterized using flow cytometry and the carotid artery was measured using B-mode ultrasound to calculate T-PWV at the baseline examination in a 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 twenty-five exploratory (p-significance<0.05) immune cell subpopulations, per 1-SD increment, and arterial stiffness measures were assessed using adjusted, linear regressions. Results: For the primary analysis, higher CD4+CD28-CD57+ T-cells were associated with higher LD-PWV (?=0.04 m/s, p<0.01) after adjusting for co-variates. For the exploratory analysis, T-cell subpopulations that commonly shift with aging towards memory and differentiated/immunosenescent phenotypes were associated with greater T-PWV, S-PWV, and LD-PWV after adjusting for co-variates. Conclusions: In this cross-sectional study, several T-cell subpopulations commonly associated with aging were related with measures of arterial stiffness. Longitudinal studies that examine changes in T-cell subpopulations and measures of arterial stiffness are warranted.

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Section: Introductionmentioning

confidence: 99%

Associations of circulating T-cell subsets in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis

DeConne,

Buzkova,

Pewowaruk

et al. 2024

Preprint

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CD8⁺ T-cell metabolism is related to cerebrovascular reactivity in middle-aged adults

DeConne,

Fancher,

Edwards

et al. 2024

American Journal of Physiology-Regulatory, Integrative and Comp

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Cerebrovascular reactivity (CVR) decreases with advancing age, contributing to increased risk of cognitive impairment; however, the mechanisms underlying the age-related decrease in CVR are incompletely understood. Age-related changes to T-cells, such as impaired mitochondrial respiration increase inflammation which likely contribute peripheral and cerebrovascular dysfunction in animals. However, whether T-cell mitochondrial respiration is related to cerebrovascular function in humans is not known. Therefore, we hypothesized that peripheral T-cell mitochondrial respiration would be positively associated with cerebrovascular reactivity (CVR) and that T-cell glycolytic metabolism would be negatively associated with CVR. Twenty (20) middle-aged adults (58 ± 5 years) were recruited for this study. T-cells were separated from peripheral blood mononuclear cells. Cellular oxygen consumption rate (OCR), and extracellular acidification rate (ECAR, a marker of glycolytic activity) were measured using extracellular flux analysis. CVR was quantified using the breath-hold index (BHI) which reflects the change in blood velocity in the middle-cerebral artery (MCAv) during a 30-second breath-hold. In contrast to our hypothesis, we found that basal OCR in CD8+ T-cells (β=-0.59, R2=0.27, P=0.019) was negatively associated with BHI. However, in accordance with our hypothesis, we found that basal ECAR (β=-2.20, R2=0.29, P=0.015) and maximum ECAR (β=-50, R2=0.24, P=0.029) were negatively associated with BHI in CD8+ T-cells. There were no associations observed in CD4+ T-cells. These associations appeared to be primarily mediated by an association with the pressor response to the breath-hold test. Overall, our findings suggest that CD8+ T-cell respiration and glycolytic activity may influence cerebrovascular reactivity in humans.

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Early life thymectomy induces arterial dysfunction in mice

Cited by 2 publications

References 59 publications

Associations of circulating T-cell subsets in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis

Associations of circulating T-cell subsets in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis

CD8⁺ T-cell metabolism is related to cerebrovascular reactivity in middle-aged adults

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Early life thymectomy induces arterial dysfunction in mice

Cited by 2 publications

References 59 publications

Associations of circulating T-cell subsets in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis

Associations of circulating T-cell subsets in carotid artery stiffness: the Multi-Ethnic Study of Atherosclerosis

CD8+ T-cell metabolism is related to cerebrovascular reactivity in middle-aged adults

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Product

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CD8⁺ T-cell metabolism is related to cerebrovascular reactivity in middle-aged adults