Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation

Abstract Levels of secretory phospholipases A2 (sPLA2) highly increase under acute and chronic inflammatory conditions. sPLA2 is mainly associated with high-density lipoproteins (HDL) and generates bioactive lysophospholipids implicated in acute and chronic inflammatory processes. Unexpectedly, phar...

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Autores principales:	Sanja Curcic, Michael Holzer, Lisa Pasterk, Eva Knuplez, Thomas O. Eichmann, Saša Frank, Robert Zimmermann, Rudolf Schicho, Akos Heinemann, Gunther Marsche
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/48d7c4c6f75c4565921dcb6695e9d898
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spelling	oai:doaj.org-article:48d7c4c6f75c4565921dcb6695e9d8982021-12-02T16:06:10ZSecretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation10.1038/s41598-017-08136-12045-2322https://doaj.org/article/48d7c4c6f75c4565921dcb6695e9d8982017-08-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-08136-1https://doaj.org/toc/2045-2322Abstract Levels of secretory phospholipases A2 (sPLA2) highly increase under acute and chronic inflammatory conditions. sPLA2 is mainly associated with high-density lipoproteins (HDL) and generates bioactive lysophospholipids implicated in acute and chronic inflammatory processes. Unexpectedly, pharmacological inhibition of sPLA2 in patients with acute coronary syndrome was associated with an increased risk of myocardial infarction and stroke. Given that platelets are key players in thrombosis and inflammation, we hypothesized that sPLA2-induced hydrolysis of HDL-associated phospholipids (sPLA2-HDL) generates modified HDL particles that affect platelet function. We observed that sPLA2-HDL potently and rapidly inhibited platelet aggregation induced by several agonists, P-selectin expression, GPIIb/IIIa activation and superoxide production, whereas native HDL showed little effects. sPLA2-HDL suppressed the agonist-induced rise of intracellular Ca2+ levels and phosphorylation of Akt and ERK1/2, which trigger key steps in promoting platelet activation. Importantly, sPLA2 in the absence of HDL showed no effects, whereas enrichment of HDL with lysophosphatidylcholines containing saturated fatty acids (the main sPLA2 products) mimicked sPLA2-HDL activities. Our findings suggest that sPLA2 generates lysophosphatidylcholine-enriched HDL particles that modulate platelet function under inflammatory conditions.Sanja CurcicMichael HolzerLisa PasterkEva KnuplezThomas O. EichmannSaša FrankRobert ZimmermannRudolf SchichoAkos HeinemannGunther MarscheNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-12 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Sanja Curcic Michael Holzer Lisa Pasterk Eva Knuplez Thomas O. Eichmann Saša Frank Robert Zimmermann Rudolf Schicho Akos Heinemann Gunther Marsche Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation
description	Abstract Levels of secretory phospholipases A2 (sPLA2) highly increase under acute and chronic inflammatory conditions. sPLA2 is mainly associated with high-density lipoproteins (HDL) and generates bioactive lysophospholipids implicated in acute and chronic inflammatory processes. Unexpectedly, pharmacological inhibition of sPLA2 in patients with acute coronary syndrome was associated with an increased risk of myocardial infarction and stroke. Given that platelets are key players in thrombosis and inflammation, we hypothesized that sPLA2-induced hydrolysis of HDL-associated phospholipids (sPLA2-HDL) generates modified HDL particles that affect platelet function. We observed that sPLA2-HDL potently and rapidly inhibited platelet aggregation induced by several agonists, P-selectin expression, GPIIb/IIIa activation and superoxide production, whereas native HDL showed little effects. sPLA2-HDL suppressed the agonist-induced rise of intracellular Ca2+ levels and phosphorylation of Akt and ERK1/2, which trigger key steps in promoting platelet activation. Importantly, sPLA2 in the absence of HDL showed no effects, whereas enrichment of HDL with lysophosphatidylcholines containing saturated fatty acids (the main sPLA2 products) mimicked sPLA2-HDL activities. Our findings suggest that sPLA2 generates lysophosphatidylcholine-enriched HDL particles that modulate platelet function under inflammatory conditions.
format	article
author	Sanja Curcic Michael Holzer Lisa Pasterk Eva Knuplez Thomas O. Eichmann Saša Frank Robert Zimmermann Rudolf Schicho Akos Heinemann Gunther Marsche
author_facet	Sanja Curcic Michael Holzer Lisa Pasterk Eva Knuplez Thomas O. Eichmann Saša Frank Robert Zimmermann Rudolf Schicho Akos Heinemann Gunther Marsche
author_sort	Sanja Curcic
title	Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation
title_short	Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation
title_full	Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation
title_fullStr	Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation
title_full_unstemmed	Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation
title_sort	secretory phospholipase a2 modified hdl rapidly and potently suppresses platelet activation
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/48d7c4c6f75c4565921dcb6695e9d898
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Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation

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