Platelets and endothelial cells.
The pathogenesis of atherosclerosis, the leading cause of morbidity and mortality in industrial countries, is multifactorial. Atherogenesis, the development of atherosclerotic lesions, is initiated by a mechanical or functional injury of the endothelium. The function of the endothelium is influenced by multiple factors as a consequence of cell-cell interactions. Cell-cell communication between endothelial cells with platelets has only recently begun to receive systematic study. In recent years it has been established that platelet-endothelial interactions are involved at all stages of atherosclerotic disease. This article reviews the interactions between endothelial cells and platelets in the context of their role to initiate and accelerate atherothrombosis, as well as in acute thrombotic occlusion (e.g., at the site of atherosclerotic plaque rupture or subsequent to coronary angioplasty). From a mechanistic standpoint, platelets and endothelial cells communicate on multiple levels. Cross-talk may occur over a distance (paracrine signaling), via transient interactions (so-called give-and-go mechanism), or through receptor-mediated cell-cell adhesion. Platelets may release or transfer substances that influence endothelial cell function, and vice versa. Among many others, adhesion molecules, such as P-selectin (CD62P), are of special interest because of their role in modulating interactions between blood cells and the endothelium, and also because of the possible use of the soluble form as a plasma predictor of adverse cardiovascular events. In addition to dietary, cholesterol and lipid lowering, and other pharmaceutical approaches, antiplatelet therapy plays an important part in the treatment of atherosclerosis and its multifactorial clinical manifestations. Understanding the specific interactions between platelets and the endothelium may lead to the development of novel therapeutic strategies.
Siegel-Axel
Dorothea I
DI
Medizinische Klinik III, Eberhard Karls-Universität Tübingen, Tübingen, Germany.
Gawaz
Meinrad
M
D001157:Arterial Occlusive Diseases / Q000209:etiology / Q000628:therapy; D001792:Blood Platelets / Q000473:pathology / Q000502:physiology*; D002448:Cell Adhesion; D002450:Cell Communication / Q000502:physiology*; D042783:Endothelial Cells / Q000473:pathology / Q000502:physiology*; D004730:Endothelium, Vascular / Q000473:pathology / Q000502:physiology; D006801:Humans; D013927:Thrombosis / Q000209:etiology* / Q000628:therapy