Effects of Pyridoxamine Treatment on Large Artery Stiffness, Endothelial Function, and Cognitive Impairment in Old Mice

Abstract We have shown that T cells accumulate around the aorta with advanced age and that both pharmacologic and genetic deletion of total T cells result in improved large artery stiffness in old mice. The purpose of this study was to test the hypothesis that CD8 T cells specifically mediate age-related large artery stiffening. We randomized old (22-24 month) C57Bl6 mice (n=5/group) to treatment with an anti-CD8 or isotype control antibody (100µg every 5 days) for 28 days. We assessed large artery stiffness using pulse wave velocity (PWV) before and after antibody treatment. We found that PWV was similar between isotype (301±14 cm/s) and anti-CD8 (292±18 cm/s) before treatment. Following treatment, anti-CD8 treated mice exhibited lower PWV (272±11 cm/s) compared to the isotype (315±14 cm/s). Following euthanasia, we assessed aortic T cell infiltration by flow cytometry we found that anti-CD8 treated mice exhibited blunted aortic total CD3+ (262±42 vs. 1400±94 cells per aorta) and CD8+ (52±19 vs. 565±139 cells per aorta) cells compared to isotype controls. In a separate cohort of mice we compared interferon (IFN)-γ and tumor necrosis factor (TNF)-α production of aortic infiltrating CD8 cells from young (4-6 months, n=5) and old mice (n=8) using flow cytometry. A greater proportion of CD8 cells from old aortas produced IFN-γ (70±3% vs. 46±6%) compared to young. Similarly, a greater proportion of aortic infiltrating CD8 cells from old mice produced TNF-α (35±6% vs. 17±3%) compared to young. Collectively, these results suggest that pro-inflammatory CD8 cells contribute to cell non-autonomous arterial aging.

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Effects of GH replacement on endothelial function and large-artery stiffness in GH-deficient adults: a randomized, double-blind, placebo-controlled study

Clinical Endocrinology ◽

10.1046/j.1365-2265.2002.01514.x ◽

2002 ◽

Vol 56 (4) ◽

pp. 493-501 ◽

Cited By ~ 86

Author(s):

J. C. Smith ◽

L. M. Evans ◽

I. Wilkinson ◽

J. Goodfellow ◽

J. R. Cockcroft ◽

...

Keyword(s):

Endothelial Function ◽

Controlled Study ◽

Large Artery ◽

Double Blind ◽

Double Blind Placebo ◽

Gh Replacement ◽

Artery Stiffness

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Curcumin improves large elastic artery stiffness and reverses superoxide suppression of nitric oxide‐mediated vascular endothelial function in old mice

The FASEB Journal ◽

10.1096/fasebj.25.1_supplement.lb453 ◽

2011 ◽

Vol 25 (S1) ◽

Author(s):

Kate L Howell ◽

Bradley S. Fleenor ◽

Melanie L. Zigler ◽

Mutsuko Yoshizawa ◽

Mandy L. Marziaz ◽

...

Keyword(s):

Nitric Oxide ◽

Endothelial Function ◽

Vascular Endothelial ◽

Vascular Endothelial Function ◽

Artery Stiffness ◽

Elastic Artery ◽

Old Mice

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Sex Differences in Large Artery Stiffness: Implications for Cerebrovascular Dysfunction and Alzheimer’s Disease

Frontiers in Aging ◽

10.3389/fragi.2021.791208 ◽

2021 ◽

Vol 2 ◽

Author(s):

Mackenzie N. Kehmeier ◽

Ashley E. Walker

Keyword(s):

Alzheimer’S Disease ◽

Alzheimer's Disease ◽

Sex Differences ◽

Cognitive Impairment ◽

Disease Progression ◽

Large Artery ◽

Cerebrovascular Dysfunction ◽

Artery Stiffness ◽

Post Menopause ◽

The Impact

Two in every three Alzheimer’s disease diagnoses are females, calling attention to the need to understand sexual dimorphisms with aging and neurodegenerative disease progression. Dysfunction and damage to the vasculature with aging are strongly linked to Alzheimer’s disease. With aging there is an increase in stiffness of the large elastic arteries, and this stiffening is associated with cerebrovascular dysfunction and cognitive impairment. However, it is unclear how the deleterious effects of arterial stiffness may differ between females and males. While environmental, chromosomal, and sex hormone factors influence aging, there is evidence that the deficiency of estrogen post-menopause in females is a contributor to vascular aging and Alzheimer’s disease progression. The purpose of this mini review is to describe the recent developments in our understanding of sex differences in large artery stiffness, cerebrovascular dysfunction, and cognitive impairment, and their intricate relations. Furthermore, we will focus on the impact of the loss of estrogen post-menopause as a potential driving factor for these outcomes. Overall, a better understanding of how sex differences influence aging physiology is crucial to the prevention and treatment of neurodegenerative diseases.

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