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The role of thrombin receptors PAR1 and PAR4 for PAI-1 storage, synthesis and secretion by human platelets
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.ORCID iD: 0000-0002-5143-8315
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.ORCID iD: 0000-0002-1920-3962
Department of Clinical and Experimental Medicine, Linköping University, Linköping, Sweden.
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2012 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 129, no 4, p. E51-E58Article in journal (Refereed) Published
Abstract [en]

Introduction: Arterial thrombi contain more platelets than venous thrombi and are more resistant to fibrinolysis. This resistance could partly be due to plasminogen activator inhibitor 1 (PAI-1) secreted by platelets. The aim of this study was to elucidate differences between thrombin receptors protease-activated receptor (PAR) 1 and 4 and platelet storage, secretion and synthesis of platelet PAI-1, as compared to other platelet alpha-granule proteins such as VEGF and endostatin.

Materials and methods: Human isolated platelets were incubated with thrombin (0.5 U/ml), PAR1-activating peptide (AP) (0.4-30 mu M) or PAR4-AP (1.5-300 mu M) for up to 24 hours. ELISA, western blot and fluorescence microscopy were used to measure secretion, contents and localization of PAI-1, VEGF and endostatin. Results: Our results show that PAI-1 and VEGF might be co-localized and that endostatin does not co-localize with either PAI-1 or VEGF. PAI-1 and VEGF show a similar secretion pattern, being more sensitive to low grade PAR1 activation, but secretion was also observed with higher concentrations of PAR4-APs. PAI-1 is secreted in an active form. PAI-1 mRNA was found in platelets, and elevated levels of PAI-1 were detected after 24 hours incubation of platelets.

Conclusions: PAI-1 and VEGF, but not endostatin, might be stored in the same alpha-granule in human platelets. PAI-1 and VEGF also show a similar secretion pattern, being more sensitive to PAR1 than to PAR4 activation, but the secretion is not exclusively selective. Our results also show that platelet PAI-1 is increased if incubated for 24 hours, both with addition of PAR1-activating peptide and without activation, which could indicate de novo synthesis.

Place, publisher, year, edition, pages
Elsevier, 2012. Vol. 129, no 4, p. E51-E58
Keywords [en]
Blood Platelets, PAR1, PAR4, Plasminogen Activator Inhibitor 1, Thrombin, VEGF
National Category
Cell Biology
Identifiers
URN: urn:nbn:se:oru:diva-66161DOI: 10.1016/j.thromres.2011.12.021ISI: 000301587400010PubMedID: 22283974Scopus ID: 2-s2.0-84858333888OAI: oai:DiVA.org:oru-66161DiVA, id: diva2:1193410
Available from: 2018-03-26 Created: 2018-03-26 Last updated: 2018-05-15Bibliographically approved

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Ramström, SofiaLarsson, Anders

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