Resveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK.
AMP-Activated Protein Kinases
/ genetics
Animals
Carotid Artery Injuries
/ drug therapy
Carotid Artery, Common
/ drug effects
Diet, High-Fat
Disease Models, Animal
Femoral Artery
/ drug effects
Insulin Resistance
Mice, Knockout
Neointima
Rats, Sprague-Dawley
Resveratrol
/ pharmacology
Signal Transduction
Sirtuin 1
/ genetics
Vascular System Injuries
/ drug therapy
Carotid balloon injury
Femoral wire injury
Insulin resistance
Restenosis
Journal
Journal of vascular research
ISSN: 1423-0135
Titre abrégé: J Vasc Res
Pays: Switzerland
ID NLM: 9206092
Informations de publication
Date de publication:
2020
2020
Historique:
received:
18
03
2020
accepted:
20
05
2020
pubmed:
11
8
2020
medline:
20
1
2021
entrez:
11
8
2020
Statut:
ppublish
Résumé
We have shown that both insulin and resveratrol (RSV) decrease neointimal hyperplasia in chow-fed rodents via mechanisms that are in part overlapping and involve the activation of endothelial nitric oxide synthase (eNOS). However, this vasculoprotective effect of insulin is abolished in high-fat-fed insulin-resistant rats. Since RSV, in addition to increasing insulin sensitivity, can activate eNOS via pathways that are independent of insulin signaling, such as the activation of sirtuin 1 (SIRT1) and AMP-activated kinase (AMPK), we speculated that unlike insulin, the vasculoprotective effect of RSV would be retained in high-fat-fed rats. We found that high-fat feeding decreased insulin sensitivity and increased neointimal area and that RSV improved insulin sensitivity (p < 0.05) and decreased neointimal area in high-fat-fed rats (p < 0.05). We investigated the role of SIRT1 in the effect of RSV using two genetic mouse models. We found that RSV decreased neointimal area in high-fat-fed wild-type mice (p < 0.05), an effect that was retained in mice with catalytically inactive SIRT1 (p < 0.05) and in heterozygous SIRT1-null mice. In contrast, the effect of RSV was abolished in AMKPα2-null mice. Thus, RSV decreased neointimal hyperplasia after arterial injury in both high-fat-fed rats and mice, an effect likely not mediated by SIRT1 but by AMPKα2.
Identifiants
pubmed: 32777783
pii: 000509217
doi: 10.1159/000509217
pmc: PMC7845450
doi:
Substances chimiques
AMPK alpha2 subunit, mouse
EC 2.7.11.1
AMP-Activated Protein Kinases
EC 2.7.11.31
Sirt1 protein, mouse
EC 3.5.1.-
Sirt1 protein, rat
EC 3.5.1.-
Sirtuin 1
EC 3.5.1.-
Resveratrol
Q369O8926L
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
325-340Subventions
Organisme : NIDDK NIH HHS
ID : R01 DK091281
Pays : United States
Informations de copyright
© 2020 The Author(s) Published by S. Karger AG, Basel.
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