Protein C and the endothelium.
With the continued accumulation of clinical and animal studies, it is becoming abundantly clear that the protein C anticoagulant pathway plays a critical role in the regulation of coagulation. Investigations also indicate that this pathway is intimately involved in the interaction of the coagulation and inflammatory systems. Although no direct information is presently available, the function of this pathway is likely depressed in the regions of atherosclerotic plaque. It is clear that monocytes accumulate in this region and release many growth factors and monokines that are capable of endothelial function perturbation. Perturbation of the protein C anticoagulant pathway is one viable mechanism for the hypercoagulable state in this disease. As indicated here, the endothelial cells of the vessel wall play a critical role in the initiation, and possibly expression, of this pathway. Any injury to these cells that affects the proper expression of thrombomodulin, synthesis of protein S, or Factor Va inactivation complex formation could potentially lead to a hypercoagulable state and thrombotic complications. As has been discussed, several inflammatory mediators are already known that fulfill the criteria of endothelial cell perturbants that may lead to such a state. What other entities might have similar effects, either directly or indirectly through induction of cytokines, is not known at this time. A more complete understanding of this critical pathway and the effects of vascular disease on it should lead to a better understanding of many diverse disease processes and potential therapeutic strategies in the future.
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Cardiovascular Biology Research Program, Oklahoma Medical Research Foundation, Oklahoma City 73104.
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D000818:Animals; D001161:Arteriosclerosis / Q000097:blood*; D004730:Endothelium, Vascular / Q000378:metabolism*; D006801:Humans; D011486:Protein C / Q000378:metabolism*; D011956:Receptors, Cell Surface / Q000378:metabolism; D018179:Receptors, Thrombin; D013927:Thrombosis / Q000097:blood*
D011486:Protein C; D011956:Receptors, Cell Surface; D018179:Receptors, Thrombin