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Early life thymectomy induces arterial dysfunction in mice.

Authors
  • Buckley, David J1
  • Sharma, Sunita1
  • Joseph, Blessy1
  • Fayyaz, Alia H1
  • Canizales, Alexandra1
  • Terrebonne, Konner J1
  • Trott, Daniel W2
  • 1 Department of Kinesiology, College of Nursing and Health Innovation, The University of Texas at Arlington, 655 W. Mitchell St., Arlington, TX, 76010, USA.
  • 2 Department of Kinesiology, College of Nursing and Health Innovation, The University of Texas at Arlington, 655 W. Mitchell St., Arlington, TX, 76010, USA. [email protected].
Type
Published Article
Journal
GeroScience
Publication Date
Feb 01, 2024
Volume
46
Issue
1
Pages
1035–1051
Identifiers
DOI: 10.1007/s11357-023-00853-y
PMID: 37354388
Source
Medline
Keywords
Language
English
License
Unknown

Abstract

Aging of the arteries is characterized by increased large artery stiffness and impaired endothelium-dependent dilation. We have previously shown that in old (22-24 month) mice T cells accumulate within aorta and mesentery. We have also shown that pharmacologic and genetic deletion of these T cells ameliorates age-related arterial dysfunction. These data indicate that T cells contribute to arterial aging; however, it is unknown if aged T cells alone can induce arterial dysfunction in otherwise young mice. To produce an aged-like T cell phenotype, mice were thymectomized at three-weeks of age or were left with their thymus intact. At 9 months of age, thymectomized mice exhibited greater proportions of both CD4 + and CD8 + memory T cells compared to controls in the blood. Similar changes were observed in the T cells accumulating in the aorta and mesentery. We also observed greater numbers of proinflammatory cytokine producing T cells in the aorta and mesentery. The phenotypic T cell changes in the blood, aorta and mesentery of thymectomized mice were similar to those observed when we compared young (4-6 month) to old thymus intact mice. Along with these alterations, compared to controls, thymectomized mice exhibited augmented large artery stiffness and greater aortic collagen deposition as well as impaired mesenteric artery endothelium dependent dilation due to blunted nitric oxide bioavailability. These results indicate that early life thymectomy results in arterial dysfunction and suggest that an aged-like T cell phenotype alone is sufficient to induce arterial dysfunction in otherwise young mice. © 2023. The Author(s), under exclusive licence to American Aging Association.

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