Cholinergic regulation of vascular endothelial function by human ChAT
acetylcholine
circulation
lymphocytes
vascular biology
Journal
Proceedings of the National Academy of Sciences of the United States of America
ISSN: 1091-6490
Titre abrégé: Proc Natl Acad Sci U S A
Pays: United States
ID NLM: 7505876
Informations de publication
Date de publication:
04 04 2023
04 04 2023
Historique:
medline:
31
3
2023
entrez:
29
3
2023
pubmed:
30
3
2023
Statut:
ppublish
Résumé
Endothelial dysfunction and impaired vasodilation are linked with adverse cardiovascular events. T lymphocytes expressing choline acetyltransferase (ChAT), the enzyme catalyzing biosynthesis of the vasorelaxant acetylcholine (ACh), regulate vasodilation and are integral to the cholinergic antiinflammatory pathway in an inflammatory reflex in mice. Here, we found that human T cell ChAT mRNA expression was induced by T cell activation involving the PI3K signaling cascade. Mechanistically, we identified that ChAT mRNA expression was induced following the attenuation of RE-1 Silencing Transcription factor REST-mediated methylation of the ChAT promoter, and that ChAT mRNA expression levels were up-regulated by GATA3 in human T cells. In functional experiments, T cell-derived ACh increased endothelial nitric oxide-synthase activity, promoted vasorelaxation, and reduced vascular endothelial activation and promoted barrier integrity by a cholinergic mechanism. Further, we observed that survival in a cohort of patients with severe circulatory failure correlated with their relative frequency of
Identifiants
pubmed: 36989306
doi: 10.1073/pnas.2212476120
pmc: PMC10083572
doi:
Substances chimiques
Choline O-Acetyltransferase
EC 2.3.1.6
Phosphatidylinositol 3-Kinases
EC 2.7.1.-
Cholinergic Agents
0
Acetylcholine
N9YNS0M02X
RNA, Messenger
0
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
e2212476120Commentaires et corrections
Type : CommentIn
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