Induction of early atherosclerosis in CBA/J mice by combination of Trypanosoma cruzi infection and a high cholesterol diet

In addition to established factors such as hyperlipidemia, smoking and hype rtension, inflammation and infection have recently been implicated as major risk factors for atherosclerotic disease. Proatherogenic effects induced b y infection may be related to both systemic inflammation and to direct effe cts on the vascular wall. We report here that a high fat diet combined with a protozoal infection with known tropism to the heart induced early athero sclerosis and intimal inflammatory infiltrates (CD4(+), CD8(+) cells and ma crophages) in aortas of all (n = 7) CBA/J mice investigated. These mice are normally quite resistant to atherosclerotic development and in the control group (n = 7) receiving only a fatty diet, only one mouse presented a lesi on. This lesion was completely devoid of infiltrating CD8(+) cells. Parasit e-infected mice receiving a normal diet exhibited vasculitis, but no signs of atherosclerosis and control mice receiving normal diet, as expected, exh ibited neither signs of vasculitis nor atherosclerosis. Secretion of IL-6, TNF-alpha, and IFN-gamma were demonstrated in all atherosclerotic lesions a nd IL-6 appeared to be the dominant cytokine, both in the lesions themselve s as well as in the intimal-medial junction. There were no traces of parasi tes present in the artery wall, indicating that atherosclerosis was induced via an indirect route. We conclude that a high fat diet in conjunction wit h infection and systemic (or localized) inflammation may have a strong proa therogenic effect. Finally, we suggest that CBA/J mice infected with T. cru zi parasites and given a fatty diet could serve as a useful experimental mo del in the continued analysis of factors contributing to the induction of a therosclerosis. (C) 2000 Elsevier Science Ireland Ltd. All rights reserved.