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New light on the role of microbial pathogens in atherosclerosis

Cardiovascular disease is the leading cause of death in industrialized countries (32% of all deaths in France, for example), and atherosclerosis is often the underlying process. Genetic and environmental factors (such as smoking, obesity, hypertension and high cholesterol levels) are known to play a role in atherosclerosis, but various lines of evidence also suggest that microbial pathogens are involved in the formation of atheroma plaque (i.e. atherosclerosis) or in its rupture (potentially leading to cardiovascular events). Bacteria (especially Chlamydia pneumoniae) and viruses have been detected at an abnormally high frequency in atheroma plaque, and have been forwarded either as co-factors in people already at risk, or as the chief cause of atherosclerosis in people with none of the classical risk factors.

Alain Tedgui, Ziad Mallat (Inserm unit 141, headed by Bernard Lvy) and their coworkers found that microbial pathogens induced atherosclerosis in experimental mice when an antiinflammatory cytokine, interleukin 10 (IL-10), was lacking. IL-10 production is under genetic control. Between 50 and 60% of the human population can produce high levels of this cytokine, while 40 to 50% produce intermediate levels and 5 to 10% can only synthesize small amounts.

The Inserm team worked on a mouse strain deficient in IL-10. The animals were raised in cages with filtered air (protecting them from air-borne microbes), and received a diet designed to induce atheroma plaque. The researchers found that the plaques were three times bigger than in similarly treated mice with normal IL-10 production, thereby demonstrating that IL-10 limits atheroma plaque formation.

The team then examined what happened when IL-10-deficient mice and their normal counterparts mice were exposed to unfiltered air containing microbial pathogens. This time the atheroma plaques in the deficient mice were 30 times larger than in their IL-10-producing counterparts. In other words, exposure
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Contact: Alain Tedgui
alain.tedgui@inserm.lrb.ap-hop-paris.fr
33-1-44-63-18-60
French National Institute for Health and Medical Research (INSERM)
15-Oct-1999


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