Hypertension is traditionally considered a disease in which elevated blood pressure contributes to inflammation and activation of the immune system, leading to cardiovascular injury and end-organ damage. Here, we discuss the effects of aldosterone on the immune system and aldosterone's contribution to vascular pathogenesis. Studies in human have suggested a broader role for aldosterone, beyond elevating blood pressure. Recent clinical data support the notion that aldosterone can directly alter the function of the immune system and cause vascular-damaging inflammation. Clinical observations have been reproduced in experimental models of hypertension, further supporting the idea that an aberrant immune response contributes to the onset of hypertension. Such studies have shown that myeloid cells are required to induce the disease and IL-17-producing CD4(+) T cells may contribute to maintaining aldosterone-mediated hypertension. In addition, regulatory T cells diminish the inflammatory damage caused by aldosterone during hypertension. This is a very active area of research that could lead to new therapeutic targets for treating hypertension.

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.

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.