Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UNIPROT:P50583 (asymmetrical)
 12,197 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Thrombin generation is the culminating event of the coagulation cascade. It is initiated after the expression of tissue factor by endothelial cells and monocytes exposed to thrombogenic stimuli. Anionic phospholipids, chiefly phosphatidylserine, are necessary for the optimal activity of tissue factor and completion of the clotting process. They display a catalytic potential by allowing the formation of the characteristic enzyme complexes at the membrane surface. Platelets are viewed as the main source of procoagulant phospholipid referred to as platelet factor 3. The plasma membrane of resting cells presents an asymmetrical distribution of phospholipids, aminophospholipids being sequestered in the inner leaflet. Procoagulant phospholipids become available at the outer surface after cell stimulation. The collapse of the membrane asymmetry is thought to promote a phospholipid scrambling accompanied by the shedding of microparticles. The plasma membranes of such vesicles bear irreversibly externalized procoagulant phosphatidylserine and contain glycoproteins that testify to their tissue origin. Hence, microparticles could disseminate a dual procoagulant and adhesive potential. Thrombin autoamplification is exerted through feedback activation loops involving either coagulation factors or platelets. This article details the mechanisms by which procoagulant phospholipids promote the generation of an excess of thrombin. A new pharmacological approach of thrombosis is presented, based on the control of the exposure of procoagulant phospholipids and membrane microparticle shedding.
 ...
PMID:Physiopathological significance of catalytic phospholipids in the generation of thrombin. 880 13

Extensive studies have detailed the molecular regulation of individual components of the hemostatic system, including platelets, coagulation factors, and regulatory proteins. Questions remain, however, about how these elements are integrated at the systems level within a rapidly changing physical environment. To answer some of these questions, we developed a puncture injury model in mouse jugular veins that combines high-resolution, multimodal imaging with functional readouts in vivo. The results reveal striking spatial regulation of platelet activation and fibrin formation that could not be inferred from studies performed ex vivo. As in the microcirculation, where previous studies have been performed, gradients of platelet activation are readily apparent, as is an asymmetrical distribution of fibrin deposition and thrombin activity. Both are oriented from the outer to the inner surface of the damaged vessel wall, with a greater extent of platelet activation and fibrin accumulation on the outside than the inside. Further, we show that the importance of P2Y12 signaling in establishing a competent hemostatic plug is related to the size of the injury, thus limiting its contribution to hemostasis to specific physiologic contexts. Taken together, these studies offer insights into the organization of hemostatic plugs, provide a detailed understanding of the adverse bleeding associated with a widely prescribed class of antiplatelet agents, and highlight differences between hemostasis and thrombosis that may suggest alternative therapeutic approaches.
 ...
PMID:Interrelationships between structure and function during the hemostatic response to injury. 3067 70