Nicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling pathway
Nicotinic acid inhibits vascular inflammation via the SIRT1-dependent signaling pathway
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烟酸通过 SIRT1 依赖性信号通路抑制血管炎症
DOI：
10.1016/j.jnutbio.2015.07.006
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发表时间：
2015
影响因子：
5.6
通讯作者：
Lin Rong
中科院分区：
文献类型：
--
作者：
Li Yanxiang;Yang Guangde;Yang Xiaofeng;He Yanhao;Wang Weirong;Zhang Jiye;Li Tingting;Zhang Wei;Lin Rong
烟酸（NA）最近被证明可以抑制心血管疾病的炎症反应。Sirtuin 1（SIRT 1）是一种NAD+依赖的III类组蛋白去乙酰化酶，参与细胞炎症的调节。我们推测，饮食中补充NA可以通过调节SIRT 1通路来减轻血管炎症。新西兰白色兔接受饲料或补充有0.6%（wt/wt）NA的饲料2周。通过在左颈总动脉周围放置非闭塞性硅橡胶项圈，在动物中诱导急性血管炎症。在项圈植入后24小时，项圈诱导的C-反应蛋白和单核细胞趋化蛋白-1的产生显着抑制在NA补充动物。同时，NA还降低了分化簇40（CD 40）和CD 40配体的表达，但上调SIRT 1的表达，在兔和脂多糖刺激的内皮细胞。此外，SIRT 1的敲低逆转了NA对CD 40表达的抑制作用。进一步的研究表明，NA还通过雷帕霉素的哺乳动物靶点部分地降低了CD 40的表达。这些结果表明，NA通过SIRT 1/CD 40依赖性信号通路保护血管炎症。
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.