Niacin reduces pro-inflamatory cytokine expression in macrophages from a murine model of atherosclerosis

LIPSZYC PS; ZORRILLA-ZUBILETE MA; CREMASCHI GA; GENARO AM; WALD MR

Chicago

Congreso; American Heart Association Meeting; 2010

American Heart Association

Background: Atherosclerosis is a complex vascular pathology and is now recognized as an inflammatory disease. In fact, the current understanding of the pathogenesis of atherosclerosis includes the assignment of a critical role to cells of the monocyte/macrophage lineage. The accumulation of macrophage foam cells in atherosclerotic lesions is associated with both initiation and progression of this disease. Several cytokines have been shown to be involved in atherosclerosis, in particular pro-inflammatory cytokines. Niacin is known to improve lipid metabolism and produces beneficial modification of multiple cardiovascular risk factors. In this context, the aim of this work was to investigate if niacin could be able to modulate pro-inflammatory cytokine production in macrophages from mice subjected to atherogenic diet. Moreover the involvement of macrophage niacin receptor was also analyzed. Methods and Results: One-month old female C57Bl/6 mice were randomly assigned to two groups: one that was fed with conventional chow diet (Control, C) and the other with an atherogenic diet (AD) during 4 months. The AD group showed an increase in total plasma cholesterol, with no differences in triglyceride levels, as determined by conventional biochemical assays. Lesions in arterial walls were observed through histochemical observation. The characterization of niacin receptor in macrophages by binding with [3H]-nicotinic acid showed an increase in the receptor number in macrophages from AD group (Bmax (pmol/106 cel) C:690±85 vs AD:1331±177, p<0.01). Macrophages from C animals stimulated in vitro with IFN- plus LPS, as an inflammatory stimulus, showed elevated levels of IL-6, IL-1 and TNF- , that were even higher in macrophages from AD mice. Niacin was able to decrease the pro-inflammatory cytokine production in stimulated macrophages from both C and AD mice (Alone vs Niacin, TNF- (ng/ml), C: 3.10±0.24 vs 2.03±0.22, AD: 3.97±0.25 vs 2.24±0.23, p<0.05). Conclusions: These results demonstrate that niacin in addition to acting as a lipid-modifying drug has a beneficial action by attenuating inflammatory mechanisms involved in atherosclerosis pathology.