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Query: UMLS:C0001511 (Adhesion)
 5,955 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Type VI collagen is a subendothelial constituent that binds von Willebrand factor (vWF) and platelets. The interaction of platelets with type VI collagen and the roles of platelet glycoprotein (GP) receptors and vWF were studied under flow conditions using epi-fluorescent videomicroscopy coupled with digital image processing. We found that surface coverage was less than 6% on collagen VI at a relatively high-wall shear rate (1,000 s-1) and was approximately 60% at a low-wall shear rate (100 s-1). The molecular mechanisms involved in low-shear platelet binding were studied using monoclonal antibodies to platelet GPIb and GPIIb-IIIa, and polymeric aurin tricarboxylic acid. Anti-GPIIb-IIIa was the most effective in eliminating adhesion (surface coverage, 0.8%), followed by anti-GPIb (4.3%), and ATA (12.6%). Experiments with von Willebrand disease blood indicate that vWF is involved in platelet adhesion to collagen VI at 100 s-1. In the absence of vWF, there may be direct binding of platelet GPIIb-IIIa complexes to collagen VI. Adhesion and aggregation on collagen VI are different in shear rate dependence from collagen I. Our results suggest a possible role for collagen VI and vWF in platelet adhesion and aggregation in vascular regions with low shear rates.
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PMID:Platelet adhesion and aggregation on human type VI collagen surfaces under physiological flow conditions. 770 89

Two likely mechanisms for the initiation of arterial platelet thrombus formation under conditions of elevated fluid shear stresses are: (1) excessive adhesion and aggregation of platelets from rapidly flowing blood onto the exposed sub-endothelium of injured, atherosclerotic arteries; or (2) direct, fluid shear stress-induced aggregation of platelets in constricted arteries with intact endothelial cells. Mechanism (1) was simulated using a parallel plate flow chamber, fibrillar collagen type I-coated slides, and mepacrine-labeled (fluorescent) platelets in whole blood anticoagulated with citrate, hirudin, unfractionated porcine heparin, or low molecular weight heparin flowing for 1 to 2 minutes at wall shear rates of 100 to 3,000 seconds-1 (4 to 120 dynes/cm2). The precise sequence of interactions among von Willebrand factor (vWF), glycoprotein (GP)Ib, and GPIIb-IIIa during platelet adhesion and subsequent aggregation were resolved by direct real-time observation using a computerized epifluorescence video microscopy system. Adhesion at high shear rates was the result of the adsorption of large vWF multimers onto collagen and the binding of platelet GPIb to the insolubilized vWF. Aggregation occurred subsequently and required the binding of ligands, including vWF via its RGD binding domain, to GPIIb-IIIa. Mechanism (2) was modeled by producing shear stresses of 90 to 180 dynes/cm2 in a rotational cone and plate viscometer, which aggregates platelets from platelet-rich-plasma (PRP) anti-coagulated with citrate, hirudin, or either type of heparin in reactions that require large vWF multimers, Ca2+, adenosine diphosphate, and both GPIb and GPIIb-IIIa. Both vWF-mediated shear-aggregation in PRP and platelet-collagen adhesion in flowing whole blood (anticoagulated with citrate and hirudin) are inhibited by two potentially useful anti-arterial thrombotic agents: polymeric aurin tricarboxylic acid (ATA; 28.5 to 114 micrograms/mL), which binds to vWF and inhibits its attachment of GPIb, and a recombinant vWF fragment (rvWF445-733; 30 to 200 micrograms/mL) that binds to platelet GPIb (in the absence of any modulator) and blocks attachment of vWF multimers. Unfractionated heparin, but not low molecular weight heparin, apparently binds to rvWF445-733 and counteracts the inhibitory effects of the vWF fragment in vitro on shear-aggregation and platelet-collagen adhesion.
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PMID:Real-time analysis of shear-dependent thrombus formation and its blockade by inhibitors of von Willebrand factor binding to platelets. 844 88