Downregulation of stromal interaction molecule-1 is implicated in the age-associated vasoconstriction dysfunction of aorta, intrarenal, and coronary arteries.
Eur J Pharmacol
; 979: 176832, 2024 Sep 15.
Article
em En
| MEDLINE
| ID: mdl-39038639
ABSTRACT
The contractile function of vascular smooth muscle cells (VSMCs) typically undergoes significant changes with advancing age, leading to severe vascular aging-related diseases. The precise role and mechanism of stromal interaction molecule-1 (STIM1) in age-mediated Ca2+ signaling and vasocontraction remain unclear. The connection between STIM1 and age-related vascular dysfunction was investigated using a multi-myograph system, immunohistochemical analysis, protein blotting, and SA-ß-gal staining. Results showed that vasoconstrictor responses in the thoracic aorta, intrarenal artery, and coronary artery decreased with age. STIM1 knockdown in the intrarenal and coronary arteries reduced vascular tone in young mice, while no change was observed in the thoracic aorta. A significant reduction in vascular tone occurred in the STIM1 knockout group with nifedipine. In the thoracic aorta, vasoconstriction significantly decreased with age following the use of nifedipine and thapsigargin and almost disappeared after STIM1 knockdown. The proportion of senescent VSMCs increased significantly in aged mice and further increased in sm-STIM1 KO aged mice. Moreover, the expression of senescence markers p21, p16, and IL-6 significantly increased with age, with p21 expression further increased in the STIM1 knockdown aged group, but not p16 or IL-6. These findings indicate that different arteries exhibit distinct organ-specific features and that STIM1 downregulation may contribute to age-related vasoconstrictive dysfunction through activation of the p21 pathway.
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Base de dados:
MEDLINE
Assunto principal:
Vasoconstrição
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Envelhecimento
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Regulação para Baixo
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Vasos Coronários
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Molécula 1 de Interação Estromal
Idioma:
En
Ano de publicação:
2024
Tipo de documento:
Article