Activated Platelets Promote Formation of Atherosclerotic Lesions

Researchers working with a genetically engineered line of apolipoprotein-E–deficient mice have found that in these animals circulating activated platelets and platelet–leukocyte/monocyte aggregates promoted formation of atherosclerotic lesions, the precursors of atherosclerosis. The findings were published December 16, 2002, in the online edition of Nature Medicine.

Investigators at the University of Virginia (Charlottesville, USA) injected activated platelets into apolipoprotein-E-deficient mice and studied their interaction with aortic endothelial cells. The presence of activated platelets promoted leukocyte binding of vascular cell adhesion molecule-1 (VCAM-1) and increased their adhesiveness to inflamed or atherosclerotic endothelium. Injection of activated wild-type, but not P-selectin–deficient, platelets increased monocyte arrest on the surface of atherosclerotic lesions and the size of atherosclerotic lesions. Therefore, the role of activated platelets in atherosclerosis was attributed to platelet P-selectin–mediated delivery of platelet-derived pro-inflammatory factors to monocytes/leukocytes and the vessel wall.

"These platelets are time bombs in the blood,” explained senior author Dr. Klaus Ley, director of the Cardiovascular Research Center and professor of biomedical engineering, molecular physiology, and biological physics at the University of Virginia. "The hope now is that we can develop anti-platelet drugs to limit activation, which would be a beneficial, effective preventive measure against heart attack. These important observations could translate into improved therapies for limiting this extremely prevalent disease.”




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