ANTAGONIZING ATHEROSCLEROSIS

Antagonizing Atherosclerosis
France - Atherosclerosis or fatty plaque build up on the arterial wall is the source of most cardiovascular diseases. While B cells of the immune system were previously considered as elements of protection against the formation of these plaques, researchers from Inserm now refute this hypothesis. These findings were published online in the Journal of Experimental Medicine.

Atherosclerosis is an inflammatory disease of the arteries triggered by several factors, including increased cholesterol and characterized by an accumulation of lipids (fats) in the arterial wall in the form of plaques. The rupture of these plaques is responsible for the majority of cardiovascular diseases, like myocardial infarction or stroke. These diseases are the leading cause of death in industrialized countries. It is therefore essential to identify patients at risk and to understand the progression of the disease, to prevent and treat it.

The immune response (macrophages, B lymphocytes, T lymphocytes) which varies among
individuals plays an important role in the progression of these plaques and thus in the development of complications of cardiovascular disease. To date, the role assigned to all B cells seemed protective of atherosclerosis.

However, the work led by Ziad Mallat now clearly refute this hypothesis. The researcher showed in fact that using an antibody against B cells and causing the disappearance of 96% of
them provides significant protection against development of atherosclerosis. This antibody is
used very effectively in humans, in the treatment of certain inflammatory diseases. The protective effect is due to decreased production of an immune system hormone, interferon gamma which promotes atherosclerosis and increased interleukin-17 a protective hormone.

These findings have important clinical implications. They suggest that treatments directed against B cells currently administered to patients suffering from inflammatory diseases such as
lupus or rheumatoid arthritis, may reduce cardiovascular risk. Clinical trials have been undertaken in this direction by the team and aim to assess the extent of atherosclerosis before and after treatment.

Journal Reference:
Ait-Oufella, H., et al. B cell depletion reduces the development of atherosclerosis in mice. Journal of Experimental Medicine, 2010.
Link: http://jem.rupress.org/content/early/2010/06/30/jem.20100155