The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae
He Hu, Grant N. Pierce, Guangming Zhong
He Hu, Grant N. Pierce, Guangming Zhong
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The atherogenic effects of chlamydia are dependent on serum cholesterol and specific to Chlamydia pneumoniae

Abstract

Epidemiological investigations have linked Chlamydia pneumoniae infection to atherosclerosis. It is not clear, however, whether C. pneumoniae infection plays a causal role in the development of atherosclerosis. Mice with low-density lipoprotein receptor deficiency were induced to develop atherosclerotic lesions in aorta with a cholesterol-enriched diet that increased serum cholesterol by two- to threefold. Using this mouse model, we found that the chlamydial infection alone with either the C. pneumoniae AR39 or the C. trachomatis MoPn strain failed to induce any significant atherosclerotic lesions in aorta over a period of nine months. However, in the presence of a high-cholesterol diet, infection with the C. pneumoniae AR39 strain significantly exacerbated the hypercholesterolemia-induced atherosclerosis, demonstrating that a hypercholesterolemic condition is required for the C. pneumoniae to aggravate the development of atherosclerosis. Although both AR39 and MoPn antigens were detected in aorta of mice infected with the corresponding strains, only mice infected with the C. pneumoniae strain AR39 displayed enhanced atherosclerotic lesions, suggesting that the C. pneumoniae species may possess a unique atherogenic property. This study may provide a model for further understanding the mechanisms of C. pneumoniae atherogenesis and evaluating chlamydial intervention strategies for preventing the advancement of atherosclerotic lesions enhanced by C. pneumoniae infection.

Authors

He Hu, Grant N. Pierce, Guangming Zhong

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Quantitation of mouse aorta atherosclerosis lesions as lesion area (a an...
Quantitation of mouse aorta atherosclerosis lesions as lesion area (a and c) and intimal thickness index (b). (a) Aorta luminal surface images (as shown in Fig. 2, a–f) from the six groups of mice, as indicated at the bottom of the present figure and described in Fig. 1 legend, were analyzed using an image software for total aorta luminal surface area and areas covered with lesions. The lesion area index was calculated as percentage of aortic area covered by the atherosclerotic lesions (means ± SE) as shown along the y axis. (b) The cross-sections stained with hematoxylin and eosin as described in Fig. 2, g–l, were used for measuring the lesion intimal thickness. An average of three measurements from three independent sections of the same aorta sample was used as the intimal thickness index (means ± SE) as shown along the y axis. The AR39 infection plus high-cholesterol group (n = 7) is significantly different from the high-cholesterol alone group (n = 7) in both lesion area (a; *P < 0.001) and lesion thickness (b; #P < 0.05). (c) Comparison of aortic lesion area index from mice sacrificed at 6 months (open columns;n = 3 for each group) vs. 9 months (hatched columns; the same data as displayed in a). For columns 1 vs. 2, 1 vs. 3, 2 vs. 4, 3 vs. 4, 5 vs. 6, and 5 vs. 7, P > 0.05; for column 3 vs. 5, P < 0.05; for columns 4 vs. 6, 6 vs. 8, and 7 vs. 8,P < 0.001.