Open AccessResveratrol Inhibits Neointimal Growth after Arterial Injury in High-Fat-Fed Rodents: The Roles of SIRT1 and AMPK
Author(s) -
Jing Guo,
Troy J. Pereira,
Yusaku Mori,
Marel Gonzalez Medina,
Danna M. Breen,
Prasad S. Dalvi,
Hangjun Zhang,
Declan F. McCole,
Michael W. McBurney,
Scott P. Heximer,
Evangelia Tsiani,
Ver W. Dolinsky,
Adria Giacca
Publication year - 2020
Publication title -
journal of vascular research
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.58
H-Index - 74
eISSN - 1423-0135
pISSN - 1018-1172
DOI - 10.1159/000509217
Subject(s) - neointimal hyperplasia , medicine , endocrinology , insulin , ampk , enos , resveratrol , insulin resistance , nitric oxide , amp activated protein kinase , sirtuin 1 , chemistry , nitric oxide synthase , downregulation and upregulation , protein kinase a , kinase , restenosis , pharmacology , biochemistry , stent , gene
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.