New light on the role of microbial pathogens in atherosclerosis

October 15, 1999

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 Lévy) 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 to air-borne pathogens multiplied atheroma plaque formation by a factor of 10 in IL-10-deficient mice.

Finally, the researchers examined the composition of the atheroma plaque (proportions of lipids, macrophages, fibers and muscle cells), because this is an important factor in its stability, i.e. its tendency to break free from the vessel wall. The proportion of collagen fibers - a factor protecting against rupture - was four times lower in IL-10-deficient mice than in normal mice. Thus, the absence of IL-10 not only multiplied by a factor of 10 the size of the atheroma plaque when mice were exposed to air-borne pathogens, but it also made the plaque far more likely to rupture.

These results, published by Inserm unit 141, pave the way for studies designed to examine whether the risk of human cardiovascular disease is linked to IL-10 production capacity. They also lay the foundations for studies that may finally show whether certain microbial pathogens are involved in atherosclerosis.

If confirmed in humans, these findings may shortly lead to new treatment possibilities for atherosclerosis, as recombinant interleukin 10 is already being used to treat certain diseases.
-end-


French National Institute for Health and Medical Research (INSERM)

Related Cardiovascular Disease Articles from Brightsurf:

Changes by income level in cardiovascular disease in US
Researchers examined changes in how common cardiovascular disease was in the highest-income earners compared with the rest of the population in the United States between 1999 and 2016.

Fighting cardiovascular disease with acne drug
Researchers from the European Molecular Biology Laboratory (EMBL) in Heidelberg and Stanford University have found the cause of dilated cardiomyopathy - a leading cause of heart failure - and identified a potential treatment for it: a drug already used to treat acne.

A talk with your GP may prevent cardiovascular disease
Having a general practitioner (GP) who is trained in motivational interviewing may reduce your risk of getting cardiovascular disease.

Dilemma of COVID-19, aging and cardiovascular disease
Whether individuals should continue to take angiotensin-converting enzyme inhibitors and angiotensin receptor blockers in the context of coronavirus disease 2019 (COVID-19) is discussed in this article.

Air pollution linked to dementia and cardiovascular disease
People continuously exposed to air pollution are at increased risk of dementia, especially if they also suffer from cardiovascular diseases, according to a study at Karolinska Institutet in Sweden published in the journal JAMA Neurology.

New insights into the effect of aging on cardiovascular disease
Aging adults are more likely to have - and die from - cardiovascular disease than their younger counterparts.

Premature death from cardiovascular disease
National data were used to examine changes from 2000 to 2015 in premature death (ages 25 to 64) from cardiovascular disease in the United States.

Ultrasound: The potential power for cardiovascular disease therapy
In the current issue of Cardiovascular Innovations and Applications volume 4, issue 2, pp.

Despite the ACA, millions of Americans with cardiovascular disease still can't get care
Cardiovascular disease (CVD) is the leading cause of death for Americans, yet millions with CVD or cardiovascular risk factors (CVRF) still can't access the care they need, even years after the implementation of the Affordable Care Act (ACA).

Excess weight and body fat cause cardiovascular disease
In the first Mendelian randomization study to look at this, researchers have found evidence that excess weight and body fat cause a range of heart and blood vessel diseases (rather than just being associated with it).

Read More: Cardiovascular Disease News and Cardiovascular Disease Current Events
Brightsurf.com is a participant in the Amazon Services LLC Associates Program, an affiliate advertising program designed to provide a means for sites to earn advertising fees by advertising and linking to Amazon.com.