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The role of thrombin receptors PAR1 and PAR4 for PAI-1 storage, synthesis and secretion by human platelets
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2012 (English)In: Thrombosis Research, ISSN 0049-3848, E-ISSN 1879-2472, Vol. 129, no 4, e51-e58 p.Article 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 α-granule proteins such as VEGF and endostatin.

MATERIALS AND METHODS:

Human isolated platelets were incubated with thrombin (0.5U/ml), PAR1-activating peptide (AP) (0.4-30μM) or PAR4-AP (1.5-300μM) for up to 24hours. 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 24hours incubation of platelets.

CONCLUSIONS:

PAI-1 and VEGF, but not endostatin, might be stored in the same α-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 24hours, both with addition of PAR1-activating peptide and without activation, which could indicate de novo synthesis.

Place, publisher, year, edition, pages
2012. Vol. 129, no 4, e51-e58 p.
National Category
Clinical Laboratory Medicine
Identifiers
URN: urn:nbn:se:uu:diva-168691DOI: 10.1016/j.thromres.2011.12.021ISI: 000301587400010PubMedID: 22283974OAI: oai:DiVA.org:uu-168691DiVA: diva2:503189
Available from: 2012-02-15 Created: 2012-02-15 Last updated: 2017-12-07Bibliographically approved

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Larsson, Anders

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