Atherosclerosis is a Greek term used to describe the process by which a variety of material, including fatty substances, cholesterol, cellular waste products and calcium build up in the lining of arteries. This buildup forms plaques that can then rupture leading to heart attacks and strokes.
Gwen Randolph, Assistant Professor of Gene and Cell Medicine at Mount Sinai School of Medicine and colleagues report that immune cells that are drawn to the site of a plaque may end up getting caught by lipid compounds in the plaque. The immune cells presence in the plaque then attracts more immune cells, setting up a cycle that leads to continued progression of the disease.
After being recruited to a site of injury or infection, a fraction of monocytes - a type of white blood cell - take up permanent residence there. Others are converted into mobile cells that migrate via the lymphatic system. Normally, this immigration and emigration of monocytes sets up a state of homeostasis in tissues. However, in atherosclerosis, this balance is upset and more cells end up staying in the plaque then leaving. The researchers examined the movement of monocyte-derived cells across blood vessel walls in vitro. They found that two lipid mediators - ly sophosphatidic acid and platelet-activating factor - blocked the conversion of monocytes into migratory cells and prevented their emigration from the tissue. The researchers also found that emigration from lesions was impaired in progressive atherosclerotic lesions in mice, confirming their in vitro findings.
This research suggests that an alteration in factors that normally allow monocytes to differentiate into migratory cells may lead to their buildup in atherosclerotic plaques. Since monocyte-derived cells in tissues recruit even more immune cells to the lesion, this disruption may promote plaque progression and the development of heart disease.
Proceedings of the National Academy of Sciences