Native macromolecular heparin proteoglycans exocytosed from stimulated rat serosal mast cells strongly inhibit platelet-collagen interactions

Arteriosclerosis, Thrombosis, and Vascular Biology
R LassilaP T Kovanen

Abstract

Mast cells, the major source of tissue heparin, line the vascular system. On stimulation, rat serosal mast cells release soluble heparin proteoglycans (HEP-PGs) of very high molecular weight (7500(K)). We compared the effects of HEP-PGs and standard heparins (average molecular weights, 15,000 and 5,000) on platelet-collagen interactions in vitro. In contrast with the standard heparins, HEP-PGs completely inhibited collagen-induced platelet aggregation and serotonin release in platelet-rich plasma. The inhibition caused by HEP-PGs depended on its macromolecular structure. In flowing blood, HEP-PGs also inhibited platelet deposition on a collagen-coated surface both at low and high shear rates. Although HEP-PGs did not block glycoprotein (GP) Ia/IIa-mediated platelet adhesion, they attenuated subsequent platelet activation and aggregation, as well as fibrinogen binding to platelets after collagen stimulation. HEP-PGs did not bind to platelets but bound tightly to von Willebrand factor (vWf) and enhanced its binding to collagen. Although platelet adhesion at high shear rate and vWf binding to GP Ib after ristocetin stimulation were not markedly affected, HEP-PGs reduced thrombin-induced aggregation and vWf binding to GP IIb/IIIa. ...Continue Reading

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Citations

Jul 25, 2000·Molecular Medicine Today·J L KelleyG Krishnaswamy
Aug 12, 1999·British Journal of Haematology·C GardinerS J Machin
Jul 14, 2016·Clinical and Experimental Nephrology·Raimo TuuminenRiitta Lassila
May 15, 2007·Immunological Reviews·Petri T Kovanen
Sep 1, 2007·Journal of Cellular and Molecular Medicine·Ken A LindstedtPetri T Kovanen
Oct 9, 2015·Medicine·Ana B CarvalhosaMarie-Olivia Chandesris
Sep 14, 2019·International Journal of Molecular Sciences·Petri T Kovanen
Feb 28, 2021·American Journal of Hematology·Chrysovalantou ChatzidimitriouTheodoros P Vassilakopoulos
Jun 17, 2021·Journal of Cardiovascular Pharmacology·Simon CraigeRiitta Lassila
Nov 14, 2021·Analytical and Bioanalytical Chemistry·Maximilian WinzelyGernot Friedbacher

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