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 hypertension, inflammation and infection have recently been implicated as major risk factors for atherosclerotic disease. Proatherogenic effects induced by infection may be related to both systemic inflammation and to direct effects 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 atherosclerosis and intimal inflammatory infiltrates (CD4+, CD8+ cells and macrophages) 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 lesion. This lesion was completely devoid of infiltrating CD8+ cells. Parasite-infected mice receiving a normal diet exhibited vasculitis, but no signs of atherosclerosis and control mice receiving normal diet, as expected, exhibited neither signs of vasculitis nor atherosclerosis. Secretion of IL-6, TNF-alpha, and IFN-gamma were demonstrated in all atherosclerotic lesions and IL-6 appeared to be the dominant cytokine, both in the lesions themselves as well as in the intimal-medial junction. There were no traces of parasites present in the artery wall, indicating that atherosclerosis was induced via an indirect route. We conclude that a high fat diet in conjunction with infection and systemic (or localized) inflammation may have a strong proatherogenic effect. Finally, we suggest that CBA/J mice infected with T. cruzi parasites and given a fatty diet could serve as a useful experimental model in the continued analysis of factors contributing to the induction of atherosclerosis.
Sunnemark
D
D
Microbiology and Tumorbiology Center MTC, Karolinska Institutet, Stockholm, Sweden. dan.sunnemark@mtc.ki.se
Harris
R A
RA
Frostegård
J
J
Orn
A
A
D000818:Animals; D001161:Arteriosclerosis / Q000209:etiology* / Q000276:immunology / Q000378:metabolism / Q000382:microbiology; D002791:Cholesterol, Dietary / Q000009:adverse effects*; D004195:Disease Models, Animal; D004198:Disease Susceptibility; D007249:Inflammation; D008297:Male; D051379:Mice; D008808:Mice, Inbred CBA; D014349:Trypanosoma cruzi / Q000276:immunology; D014352:Trypanosomiasis / Q000276:immunology
D002791:Cholesterol, Dietary