PMID- 11073864 OWN - NLM STAT- MEDLINE DCOM- 20001207 LR - 20190831 IS - 1524-4636 (Electronic) IS - 1079-5642 (Linking) VI - 20 IP - 11 DP - 2000 Nov TI - Coimmobilized native macromolecular heparin proteoglycans strongly inhibit platelet-collagen interactions in flowing blood. PG - E113-9 AB - We coimmobilized mast cell-derived heparin proteoglycans (HEP-PGs) of very high molecular weight (750 kDa) or unfractionated heparin (UFH) on coverslips together with collagen without altering the amount of immobilized collagen. Subsequently, platelet-collagen interactions were studied under both flowing and static conditions in D-phenylalanyl-L-prolyl-L-arginine chloromethyl ketone-anticoagulated blood and platelet-rich plasma (PRP), respectively. At a high shear rate (1600 1/s), the mean platelet deposition (PD) on collagen monomers was 7.5+/-6.1x10(6)/cm(2) (n=5). When the monomers were coimmobilized with UFH, PD was inhibited by 73% (2.0+/-1.2x10(6)/cm(2)), whereas HEP-PG completely blocked it (0. 42+/-0.38x10(6)/cm(2); P<0.05). Also, when collagen fibrils were used for coating, HEP-PG significantly inhibited PD. At a low shear rate (200 1/s) and under static conditions in PRP, the inhibitory effect of HEP-PG on PD was less marked. Inhibition of glycoprotein IIb/IIIa did not affect PD on coimmobilized HEP-PG in contrast to coimmobilized UFH or collagen alone. As a sign of inactivation, platelets adhering to the HEP-PG surface released considerably less beta-thromboglobulin than did those adhering to pure collagen. In summary, immobilized HEP-PG strongly inhibited PD on collagen by attenuating adhesion-induced platelet activation. The stronger effect on collagen monomers suggests the inhibition of glycoprotein Ia/IIa-mediated activation. FAU - Kauhanen, P AU - Kauhanen P AD - Wihuri Research Institute, Helsinki, Finland. FAU - Kovanen, P T AU - Kovanen PT FAU - Lassila, R AU - Lassila R LA - eng PT - Journal Article PT - Research Support, Non-U.S. Gov't PL - United States TA - Arterioscler Thromb Vasc Biol JT - Arteriosclerosis, thrombosis, and vascular biology JID - 9505803 RN - 0 (Glycosaminoglycans) RN - 0 (Heparan Sulfate Proteoglycans) RN - 0 (Macromolecular Substances) RN - 0 (Platelet Aggregation Inhibitors) RN - 0 (beta-Thromboglobulin) RN - 0 (von Willebrand Factor) RN - 9005-49-6 (Heparin) RN - 9007-34-5 (Collagen) SB - IM MH - Animals MH - Blood Flow Velocity MH - Blood Platelets/chemistry/*metabolism MH - Collagen/*antagonists & inhibitors/*blood MH - Glycosaminoglycans/blood MH - Heparan Sulfate Proteoglycans/*blood/isolation & purification/*physiology MH - Heparin/blood/pharmacology MH - Humans MH - Macromolecular Substances MH - Mast Cells/chemistry MH - Perfusion MH - Platelet Aggregation Inhibitors/blood/*pharmacology MH - Rats MH - beta-Thromboglobulin/metabolism MH - von Willebrand Factor/metabolism EDAT- 2000/11/14 11:00 MHDA- 2001/02/28 10:01 CRDT- 2000/11/14 11:00 PHST- 2000/11/14 11:00 [pubmed] PHST- 2001/02/28 10:01 [medline] PHST- 2000/11/14 11:00 [entrez] AID - 10.1161/01.atv.20.11.e113 [doi] PST - ppublish SO - Arterioscler Thromb Vasc Biol. 2000 Nov;20(11):E113-9. doi: 10.1161/01.atv.20.11.e113.