Nicotinamide Prevents Apolipoprotein B-Containing Lipoprotein Oxidation, Inflammation and Atherosclerosis in Apolipoprotein E-Deficient Mice.

The potential of nicotinamide (NAM) to prevent atherosclerosis has not yet been examined. This study investigated the effect of NAM supplementation on the development of atherosclerosis in a mouse model of the disease. The development of aortic atherosclerosis was significantly reduced (NAM low dose: 45%; NAM high dose: 55%) in NAM-treated, apolipoprotein (Apo)E-deficient mice challenged with a Western diet for 4 weeks. NAM administration significantly increased (1.8-fold) the plasma concentration of proatherogenic ApoB-containing lipoproteins in NAM high-dose (HD)-treated mice compared with untreated mice. However, isolated ApoB-containing lipoproteins from NAM HD mice were less prone to oxidation than those of untreated mice. This result was consistent with the decreased (1.5-fold) concentration of oxidized low-density lipoproteins in this group. Immunohistochemical staining of aortas from NAM-treated mice showed significantly increased levels of IL-10 (NAM low-dose (LD): 1.3-fold; NAM HD: 1.2-fold), concomitant with a significant decrease in the relative expression of TNFα (NAM LD: -44%; NAM HD: -57%). An improved anti-inflammatory pattern was reproduced in macrophages cultured in the presence of NAM. Thus, dietary NAM supplementation in ApoE-deficient mice prevented the development of atherosclerosis and improved protection against ApoB-containing lipoprotein oxidation and aortic inflammation.

Integrating the roles of liver X receptors in inflammation and infection: mechanisms and outcomes.

Liver X receptors (LXRs) are transcription factors from the nuclear receptor family that can be pharmacologically activated by high-affinity agonists. LXR activation exerts a combination of metabolic and anti-inflammatory actions that result in the modulation of immune responses and in the amelioration of inflammatory disorders. In addition, LXR agonists modulate the metabolism of infected cells and limit the infectivity and/or growth of several pathogens. This review gives an overview of the recent advances in understanding the complexity of the mechanisms through which the LXR pathway controls inflammation and host-cell pathogen interaction.