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/...

We studied the effects of a-tocopheryl acetate supplementation on the development of fatty streaks and its ability to modulate the expression of monocyte chemoattractant protein (MCP)-1 in aortic lesions of apoliprotein E knockout mice. For this purpose, 16-week-old apolipoprotein E knockout mice received a-tocopherol supplemention (800 mg)/kg diet) for 6 weeks. After this time, total and lipoprotein cholesterol in the serum, hepatic tocopherol, aortic lesion area and MCP-1 (protein and mRNA) expression were analysed. Our present results showed that the dietary supplementation with a-tocopherol did not reduce serum cholesterol nor change lipoprotein profile, but it reduced the area of the aortic lesion by 55 %. The reduction in the lesion size was correlated with the reduced expression of MCP-1 mRNA and protein, as detected by real-time quantitative polymerase chain reaction and immunohistochemistry respectively. In conclusion, the results obtained here are relevant to the study of atherosclerosis, as they correlate the effectiveness of vitamin E supplementation in inhibiting the plaque formation with diminished expression of MCP-1 at the aortic lesion.

Although the role of oxidized lipoproteins is well known in atherogenesis, the role of vitamin E supplementation is still controversial. There is also little information about cholesterol metabolism (hepatic concentration and fecal excretion) in the new models of atherosclerosis. In the present study, we evaluated the effect of moderate vitamin E supplementation on cholesterol metabolism and atherogenesis in apolipoprotein E (apo E)-deficient mice. Apo E-deficient mice were fed an atherogenic diet containing 40 or 400 mg/kg of = -tocopherol acetate for 6 weeks. Total cholesterol in serum and liver and 3-OH-=-sterols in feces, and fecal excretion of bile acids were determined and histological analyses of aortic lesion were performed. A vitamin Erich diet did not affect body weight, food intake or serum cholesterol. Serum and hepatic concentrations of cholesterol as well as sterol concentration in feces were similar in both groups. However, when compared to controls, the = -tocopherol-treated mice showed a reduction of about 60% in the atherosclerotic lesions when both the sum of lesion areas and the average of the largest lesion area were considered. These results demonstrate that supplementation of moderate doses of = -tocopherol was able to slow atherogenesis in apo E-deficient mice and to reduce atherogenic lipoproteins without modifying the hepatic pool or fecal excretion of cholesterol and bile acids.

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