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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2000;20:e113.)
© 2000 American Heart Association, Inc.

Thrombosis

Coimmobilized Native Macromolecular Heparin Proteoglycans Strongly Inhibit Platelet-Collagen Interactions in Flowing Blood

Petteri Kauhanen; Petri T. Kovanen; Riitta Lassila

From the Wihuri Research Institute, Helsinki, Finland (P.K., P.T.K., R.L.), and Helsinki University Central Hospital, Department Internal Medicine (R.L.).

Correspondence to Dr Riitta Lassila, Wihuri Research Institute, Kalliolinnantie 4, FIN-00140, Helsinki, Finland. E-mail riitta.lassila{at}wri.fimnet.fi

Abstract—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±6.1x10⁶/cm² (n=5). When the monomers were coimmobilized with UFH, PD was inhibited by 73% (2.0±1.2x10⁶/cm²), whereas HEP-PG completely blocked it (0.42±0.38x10⁶/cm²; 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 ß-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.

Key Words: collagen • heparin proteoglycans • mast cells • platelets