Open AccessSecretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation
Author(s) -
Sanja Ćurčić,
Michael Holzer,
Lisa Pasterk,
Eva Knuplez,
Thomas O. Eichmann,
Saša Frank,
R. Zimmermann,
Rudolf Schicho,
Ákos Heinemann,
Gunther Marsche
Publication year - 2017
Publication title -
scientific reports
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.24
H-Index - 213
ISSN - 2045-2322
DOI - 10.1038/s41598-017-08136-1
Subject(s) - lysophosphatidylcholine , platelet activation , platelet , chemistry , inflammation , phospholipase a2 , endocrinology , medicine , phospholipase , pharmacology , biochemistry , phospholipid , enzyme , membrane , phosphatidylcholine
Levels of secretory phospholipases A 2 (sPLA 2 ) highly increase under acute and chronic inflammatory conditions. sPLA 2 is mainly associated with high-density lipoproteins (HDL) and generates bioactive lysophospholipids implicated in acute and chronic inflammatory processes. Unexpectedly, pharmacological inhibition of sPLA 2 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 sPLA 2 -induced hydrolysis of HDL-associated phospholipids (sPLA 2 -HDL) generates modified HDL particles that affect platelet function. We observed that sPLA 2 -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. sPLA 2 -HDL suppressed the agonist-induced rise of intracellular Ca 2+ levels and phosphorylation of Akt and ERK1/2, which trigger key steps in promoting platelet activation. Importantly, sPLA 2 in the absence of HDL showed no effects, whereas enrichment of HDL with lysophosphatidylcholines containing saturated fatty acids (the main sPLA 2 products) mimicked sPLA 2 -HDL activities. Our findings suggest that sPLA 2 generates lysophosphatidylcholine-enriched HDL particles that modulate platelet function under inflammatory conditions.