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Toxoplasma gondii is an intracellular protozoan that elicits a potent inflammatory response during the acute phase of infection. Herein, we evaluate whether T. gondii infection alters the natural course of aortic lesions. ApoE knockout mice were infected with T. gondii, and at 5 weeks of infection, serum, feces, and liver cholesterol; aortic lesion size, cellularity, and inflammatory cytokines; and levels of serum nitrite and gamma interferon (IFN-␥) were analyzed. Our results showed that serum cholesterol and atherogenic lipoproteins were reduced after T. gondii infection. The reduction of serum levels of total cholesterol and atherogenic lipoproteins was associated with increases in the aortic lesion area, numbers of inflammatory cells, and expression of monocyte chemoattractant protein 1 and inducible nitric oxide synthase mRNA in the site of lesions as well as elevated concentrations of IFN-␥ and nitrite in sera of T. gondii-infected animals. These results suggest that infection with T. gondii accelerates atherosclerotic development by stimulating the proinflammatory response and oxidative stress, thereby increasing the area of aortic lesion.Atherosclerotic lesions are characterized by progressive accumulation of lipids, macrophages, natural killer (NK) cells, T and B cells, smooth muscle cells, and fibroproliferative elements in the intima of arteries (30). However, hypercholesterolemia and, mainly, high serum levels of low-density lipoprotein (LDL) are considered an absolute prerequisite for lesion establishment. Several genetic and environmental risk factors have been found to contribute to the development of atherosclerosis (2,22,27,33). Among these factors, the immune system is one of the most important. Innate and adaptive immune responses modulate both the rate of lesion progression and composition of atherosclerotic lesions. ApoE knockout (KO) mice crossed into a recombination activating gene (Rag)-deficient background, which lack B and T lymphocytes, had an 80% decrease in the extension of atherosclerotic lesions (32). In addition, crosses of ApoE KO mice with different types of B-or T-cell-deficient mice also decreased atherosclerotic lesions (2,22,40). Inflammatory cytokines and chemokines, such as gamma interferon (IFN-␥), tumor necrosis factor alpha (TNF-␣), TNF-␤, interleukin-12 (IL-12), IL-1␤, and monocyte chemoattractant protein 1 (MCP-1), increase the influx of monocyte into the endothelium, an important step in fatty streak formation (21,24,39). Therefore, atherosclerosis is now considered a chronic inflammatory disease, and systemic infections are thought to play an important role in initiating and/or perpetuating the pathophysiology of aortic lesions. In fact, some studies indicate that bacterial and viral pathogens could be responsible for atherosclerotic development (35). Sunnemark et al. (37) have shown that the combination of an infection of the protozoan parasite Trypanosoma cruzi with an atherogenic diet induced atherosclerotic lesions in the aorta of atherosclerosis-resistant CBA/...

Atherosclerosis and toxoplasmosis are two widely prevalent diseases worldwide. The relationship between these diseases is now being elucidated. Atherosclerosis is a disease with three main components: increased blood lipoprotein/cholesterol and their deposition in the arterial wall, an important Th1-mediated proinflammatory reaction and thrombogenic status. Toxoplasma gondii, in turn, is dependent on host cholesterol for optimal intracellular growth and replication. As a result, host cholesterol will be cleared from the blood, reducing plasma low-density lipoprotein, a crucial atherosclerosis risk factor. On the other hand, T. gondii infection elicits an important Th1 systemic inflammatory response in the host. Therefore, this additional proinflammatory stimulus may impose an enhanced pro-atherogenic environment in the host. As result, the association between these two diseases in one individual could change the course of atherosclerosis. In this review, we demonstrate that the host-parasite relationship is complex and that the outcome of each disease is dependent on the availability of intracellular cholesterol, as well as the intensity of the inflammatory reaction triggered by the parasite. We also discuss the possible clinical implications of these studies.

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Elevated blood cholesterol is an important risk factor associated with atherosclerosis and coronary heart disease. Several studies have reported a decrease in serum cholesterol during the consumption of large doses of fermented dairy products or lactobacillus strains. The proposed mechanism for this effect is the removal or assimilation of intestinal cholesterol by the bacteria, reducing cholesterol absorption. Although this effect was demonstrated in vitro, its relevance in vivo is still controversial. Furthermore, few studies have investigated the role of lactobacilli in atherogenesis. The aim of the present study was to determine the effect of Lactobacillus delbrueckii on cholesterol metabolism in germ-free mice and the possible hypocholesterolemic and antiatherogenic action of these bacteria using atherosclerosis-prone apolipoprotein E (apo E) knock-out (KO) mice. For this purpose, Swiss/NIH germ-free mice were monoassociated with L. delbrueckii and fed a hypercholesterolemic diet for four weeks. In addition, apo E KO mice were fed a normal chow diet and treated with L. delbrueckii for 6 weeks. There was a reduction in cholesterol excretion in germfree mice, which was not associated with changes in blood or liver cholesterol concentration. In apo E KO mice, no effect of L. delbrueckii was detected in blood, liver or fecal cholesterol. The atherosclerotic lesion in the aorta was also similar in mice receiving or not these bacteria. In conclusion, these results suggest that, although L. delbrueckii treatment was able to reduce cholesterol excretion in germ-free mice, no hypocholesterolemic or antiatherogenic effect was observed in apo E KO mice. Correspondence

Leishmania major infection of resistant mice causes a self-limited lesion characterized by macrophage activation and a Th1 proinflammatory response. Atherosclerosis is an inflammatory disease involving hypercholesterolemia and macrophage activation. In this study, we evaluated the influence of L. major infection on the development of atherosclerosis using atherosclerosis-susceptible apolipoprotein E-deficient (apoE KO) mice. After 6 weeks of infection, apoE KO mice exhibited reduced footpad swelling and parasitemia similar to C57BL/6 controls, confirming that both strains are resistant to infection with L. major. L. major-infected mice had increased plasma cholesterol levels and reduced triacylglycerols. With regard to atherosclerosis, noninfected mice developed only fatty streak lesions, while the infected mice presented with advanced lesions containing a necrotic core and an abundant inflammatory infiltrate. CD36 expression was increased in the aortic valve of the infected mice, indicating increased macrophage activation. In conclusion, L. major infection, although localized and self-limited in resistant apoE KO mice, has a detrimental effect on the blood lipid profile, increases the inflammatory cell migration to atherosclerotic lesions, and promotes atherogenesis. These effects are consequences of the stimulation of the immune system by L. major, which promotes the inflammatory components of atherosclerosis, which are primarily the parasite-activated macrophages.

OBJETIVO: Observar os efeitos da goma guar parcialmente hidrolisada no metabolismo de colesterol e na formação de placa aterosclerótica em aorta de camundongos deficientes no receptor LDL, euglicêmicos ou com hiperglicemia induzida por estreptozotocina. MÉTODOS: Trinta e seis camundongos deficientes para o receptor de LDL foram divididos em quatro grupos de nove animais: grupos euglicêmicos, alimentados com dieta aterogênica padrão (controle euglicêmico) ou suplementada com 7,5% de goma guar parcialmente hidrolisada (goma guar parcialmente hidrolisada euglicêmico) e grupos hiperglicêmicos alimentados com dieta aterogênica padrão (controle hiperglicêmico) ou suplementada com 7,5% de goma guar parcialmente hidrolisada (goma guar parcialmente hidrolisada hiperglicêmico). Após quatro semanas de experimento foram medidos: ingestão alimentar, ganho de peso, glicemia, colesterol plasmático e hepático, assim como lesão aterosclerótica na aorta torácica e abdominal. RESULTADOS: Os resultados mostram que a suplementação de goma guar parcialmente hidrolisada levou ao aumento do colesterol hepático e plasmático em animais euglicêmicos, mas sem aumento na área de lesão aterosclerótica na aorta. Em animais hiperglicêmicos, a redução no colesterol plasmático não foi estatisticamente significante, mas no que se refere à lesão da aorta, observou-se redução significante. CONCLUSÃO: Os resultados sugerem que a goma guar parcialmente hidrolisada pode reduzir a aterosclerose associada ao Diabetes Mellitus tipo 1.