Niacin inhibits vascular inflammation via downregulating nuclear transcription factor-κB signaling pathway.

Yanhong Si,Jilong Zhao,Ying Zhang,Shoudong Guo,Guohua Song,Lei Zhai,Jue Gu,Nana Yang,Shucun Qin,Hui Sang,Shutong Yao

doi:10.1155/2014/263786

Abstract

The study aimed to investigate the effect of niacin on vascular inflammatory lesions in vivo and in vitro as well as its lipid-regulating mechanism. In vivo study revealed that niacin downregulated the levels of inflammatory factors (IL-6 and TNF-α) in plasma, suppressed protein expression of CD68 and NF-κB p65 in arterial wall, and attenuated oxidative stress in guinea pigs that have been fed high fat diet. In vitro study further confirmed that niacin decreased the secretion of IL-6 and TNF-α and inhibited NF-κB p65 and notch1 protein expression in oxLDL-stimulated HUVECs and THP-1 macrophages. Moreover, niacin attenuated oxLDL-induced apoptosis of HUVECs as well. In addition, niacin significantly lessened lipid deposition in arterial wall, increased HDL-C and apoA levels and decreased TG and non-HDL-C levels in plasma, and upregulated the mRNA amount of cholesterol 7α-hydroxylase A1 in liver of guinea pigs. These data suggest for the first time that niacin inhibits vascular inflammation in vivo and in vitro via downregulating NF-κB signaling pathway. Furthermore, niacin also modulates plasma lipid by upregulating the expression of factors involved in the process of reverse cholesterol transport.

Highlights

Compared with chow diet group (CD) group, high fat diet for 8 weeks lightly increased the levels of C-reactive protein (CRP), IL-6, and TNF-α in plasma, but the increase was not statistically significant (P > 0.05)
The results showed that oxLDL markedly increased the protein levels of active NF-κB p65 and notch1 in HUVECs, which were suppressed by preincubation of cells with niacin in a dose-dependent manner (Figures 4(d), 4(e), 4(f), and 4(g))
Activated macrophages increase the expression of cellular adhesion molecules (CAMs) and cytokines, which results in recruitment of more leukocytes into the arterial wall, activates the complement pathways of immune system and the acute phase response, stimulates proliferation and migration of smooth muscle cells (SMCs), and promotes fibrous tissue deposition [18]

Summary

Introduction

Niacin (nicotinic acid, vitamin B3) is a water-soluble vitamin. In 1955, Altschul et al reported for the first time that pharmacological doses of niacin can lower plasma cholesterol level in normal persons as well as hypercholesterolemic patients [1]. Niacin alone or in combination can slow or reverse the progression of atherosclerosis (AS) and reduce cardiovascular event rates and total mortality in patients with hypercholesterolemia and atherosclerotic cardiovascular disease [2, 3]. These effects are generally attributed to favorable actions on the lipoprotein profile, which includes LDL-C reduction and HDL-C elevation. It is not clear whether the beneficial effects of niacin on cardiovascular disease can be completely explained by alterations of plasma lipids

Methods

Results

Conclusion