Role of inflammatory mediators in thrombogenesis.
The role of inflammation in cardiovascular disease and especially in thrombogenesis has become increasingly recognized as an important component of the overall disease process. Plaque rupture promotes activation of the inflammatory response and increased expression of tissue factor (TF), which in turn acts as one of the major initiators of extrinsic coagulation. It is becoming apparent that the expression of TF on endothelial cells, underlying smooth muscle cells and monocytes is regulated, in part, by proinflammatory cytokines including tumor necrosis factor and IL-1. In addition to initiating coagulation, interaction of TF with the adhesion molecule, P-selectin, has been demonstrated to accelerate the rate and extent of fibrin formation and deposition. P-selectin is expressed on activated platelets and endothelium and serves as the receptor for the endogenous ligand, P-selectin glycoprotein-1 (PSGL-1), expressed on various leukocytic cell types. In addition to mediating transient interactions between endothelial cells and leukocytes, P-selectin has been reported to mediate adherence of platelets to monocytes and neutrophils via specific interaction with PSGL-1. P-selectin is rapidly cleaved off the surface of the platelet membrane and appears in the circulation as a soluble form, which has been reported to be elevated in patients with acute coronary syndromes including unstable angina and non-Q-wave myocardial infarction. This review will focus on the role of cytokines in mediating TF expression and also explore the significance of the relationship between P-selectin and tissue factor in thrombus generation. In addition, possible pharmacological mechanisms to interrupt this disease process will be discussed.
Shebuski
Ronald J
RJ
CarePoint Diagnostics, Inc., Eden Prairie, Minnesota 55344, USA. CVR2000@portup.com
Kilgore
Kenneth S
KS
D000818:Animals; D016207:Cytokines / Q000037:antagonists & inhibitors / Q000502:physiology; D005337:Fibrin / Q000378:metabolism; D006801:Humans; D018836:Inflammation Mediators / Q000502:physiology*; D019007:P-Selectin / Q000502:physiology; D013925:Thromboplastin / Q000037:antagonists & inhibitors / Q000502:physiology; D013927:Thrombosis / Q000503:physiopathology* / Q000517:prevention & control
D016207:Cytokines; D018836:Inflammation Mediators; D019007:P-Selectin; D005337:Fibrin; D013925:Thromboplastin