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THE ROLE OF VONWILLEBRAND-FACTOR AND FIBRINOGEN IN PLATELET-AGGREGATION UNDER VARYING SHEAR-STRESS
Author(s): IKEDA Y, HANDA M, KAWANO K, KAMATA T, MURATA M, ARAKI Y, ANBO H, KAWAI Y, WATANABE K, ITAGAKI I, SAKAI K, RUGGERI ZM
Source: JOURNAL OF CLINICAL INVESTIGATION    Volume: 87    Issue: 4    Pages: 1234-1240    Published: APR 1991  
Times Cited: 461     References: 45     
Abstract: Exposure of platelets to shear stress leads to aggregation in the absence of exogenous agonists. We have now found that different adhesive proteins and platelet membrane glycoproteins are involved in aggregation depending on the shear stress conditions and the concentration of divalent cations in the medium. When blood is collected with trisodium citrate as anticoagulant, which causes a decrease in the levels of external ionized calcium ([Ca2+]0), platelet aggregation can be induced under low shear force (12 dyn/cm2) and is mediated by fibrinogen binding to the glycoprotein IIb-IIIa complex. Aggregates formed under these conditions are not stable, and when shear force is increased to 68 dyn/cm2, disaggregation results. By contrast, platelets from blood collected with hirudin as anticoagulant, wherein [Ca2+]0 is within normal plasma levels, do not undergo low shear-induced aggregation; however, after exposure to a shear force above 80 dyn/cm2, aggregation is observed but only when von Willebrand factor is present and can interact with both its platelet binding sites, glycoprotein Ib-IX and glycoprotein IIb-IIIa. Fibrinogen is not involved in high shear-induced aggregation which, in fact, occurs normally in patients with severe afibrinogenemia. Thus, von Willebrand factor in the absence of exogenous agonists can mediate platelet aggregation in experimental conditions that may mimic the hemorheological situation of partially occluded arteries. This pathway of platelet aggregation involving only one adhesive ligand and two membrane adhesion receptors may play a relevant role in thrombogenesis.
Document Type: Article
Language: English
Addresses:
1. SCRIPPS RES INST, DEPT MOLEC & EXPTL MED, ROON RES LAB ARTERIOSCLEROSIS & THROMBOSIS, LA JOLLA, CA 92037 USA
2. SCRIPPS RES INST, COMM VASC BIOL, LA JOLLA, CA 92037 USA
3. KEIO UNIV HOSP, DEPT INTERNAL MED, CTR BLOOD, TOKYO, JAPAN
4. KEIO UNIV HOSP, DEPT LAB MED, TOKYO, JAPAN
5. WASEDA UNIV, DEPT CHEM ENGN, TOKYO 160, JAPAN
Publisher: ROCKEFELLER UNIV PRESS, 222 E 70TH STREET, NEW YORK, NY 10021
Subject Category: Medicine, Research & Experimental
IDS Number: FE722
ISSN: 0021-9738
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