title: Nicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling pathway.
abstract: Nicotinic acid (NA) has recently been shown to inhibit inflammatory response in cardiovascular disease. Sirtuin1 (SIRT1), a NAD(+)-dependent class III histone deacetylase, participates in the regulation of cellular inflammation. We hypothesized that dietary supplementation of NA could attenuate vascular inflammation via modulation of SIRT1 pathway. New Zealand White rabbits received chow or chow supplemented with 0.6% (wt/wt) NA for 2 weeks. Acute vascular inflammation was induced in the animals by placing a non-occlusive silastic collar around the left common carotid artery. At 24 h after collar implantation, the collar-induced production of C-reactive protein and monocyte chemotactic protein-1 was significantly suppressed in the NA-supplemented animals. Meanwhile, NA also decreased the expression of cluster of differentiation 40 (CD40) and CD40 ligand, but up-regulated SIRT1 expression, both in rabbits and in lipopolysaccharide-stimulated endothelial cells. Moreover, knockdown of SIRT1 reversed the inhibitory effect of NA on CD40 expression. Further study revealed that NA also decreased the expression of CD40 partly through mammalian target of rapamycin. These results indicate that NA protects against vascular inflammation via the SIRT1/CD40-dependent signaling pathway.
authors: Department of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Cardiovascular Research Center, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors: Yanxiang
authors: Y
authors: Li
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors: Guangde
authors: G
authors: Yang
authors: Department of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors: Xiaofeng
authors: X
authors: Yang
authors: Department of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors: Yanhao
authors: Y
authors: He
authors: Laboratory Animal Center, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors: Weirong
authors: W
authors: Wang
authors: School of Pharmacy, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors: Jiye
authors: J
authors: Zhang
authors: Department of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors: Tingting
authors: T
authors: Li
authors: Department of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China.
authors: Wei
authors: W
authors: Zhang
authors: Department of Pharmacology, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China; Cardiovascular Research Center, Health Science Center, Xi'an Jiaotong University, Xi'an, Shaanxi 710061, China. Electronic address: linrong63@aliyun.com.
authors: Rong
authors: R
authors: Lin
mesh_terms: D000818:Animals; D019013:CD40 Antigens / Q000235:genetics / Q000378:metabolism; D061307:Human Umbilical Vein Endothelial Cells / Q000187:drug effects / Q000378:metabolism; D053583:Interleukin-1beta / Q000097:blood; D008055:Lipids / Q000097:blood; D008070:Lipopolysaccharides / Q000494:pharmacology; D008297:Male; D009525:Niacin / Q000494:pharmacology*; D011817:Rabbits; D015398:Signal Transduction / Q000187:drug effects; D056564:Sirtuin 1 / Q000235:genetics / Q000378:metabolism*; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D014657:Vasculitis / Q000188:drug therapy* / Q000378:metabolism*
chemical_list: D019013:CD40 Antigens; D053583:Interleukin-1beta; D008055:Lipids; D008070:Lipopolysaccharides; D009525:Niacin; C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases; C447939:SIRT1 protein, human; D056564:Sirtuin 1
keywords: Cluster of differentiation 40; Endothelium; Inflammation; Nicotinic acid; SIRT1