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Unexpectedly, pharmacological inhibition of sPLA<jats:sub>2<\/jats:sub> 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<jats:sub>2<\/jats:sub>-induced hydrolysis of HDL-associated phospholipids (sPLA<jats:sub>2<\/jats:sub>-HDL) generates modified HDL particles that affect platelet function. We observed that sPLA<jats:sub>2<\/jats:sub>-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<jats:sub>2<\/jats:sub>-HDL suppressed the agonist-induced rise of intracellular Ca<jats:sup>2+<\/jats:sup> levels and phosphorylation of Akt and ERK1\/2, which trigger key steps in promoting platelet activation. Importantly, sPLA<jats:sub>2<\/jats:sub> in the absence of HDL showed no effects, whereas enrichment of HDL with lysophosphatidylcholines containing saturated fatty acids (the main sPLA<jats:sub>2<\/jats:sub> products) mimicked sPLA<jats:sub>2<\/jats:sub>-HDL activities. Our findings suggest that sPLA<jats:sub>2<\/jats:sub> generates lysophosphatidylcholine-enriched HDL particles that modulate platelet function under inflammatory conditions.<\/jats:p>","DOI":"10.1038\/s41598-017-08136-1","type":"journal-article","created":{"date-parts":[[2017,8,8]],"date-time":"2017-08-08T08:52:28Z","timestamp":1502182348000},"update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":32,"title":["Secretory phospholipase A2 modified HDL rapidly and potently suppresses platelet activation"],"prefix":"10.1038","volume":"7","author":[{"given":"Sanja","family":"Curcic","sequence":"first","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"ORCID":"https:\/\/orcid.org\/0000-0003-3434-703X","authenticated-orcid":false,"given":"Michael","family":"Holzer","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lisa","family":"Pasterk","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Eva","family":"Knuplez","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Thomas O.","family":"Eichmann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sa\u0161a","family":"Frank","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Robert","family":"Zimmermann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Rudolf","family":"Schicho","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Akos","family":"Heinemann","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Gunther","family":"Marsche","sequence":"additional","affiliation":[],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"297","published-online":{"date-parts":[[2017,8,14]]},"reference":[{"key":"8136_CR1","doi-asserted-by":"publisher","first-page":"2183","DOI":"10.1161\/CIRCULATIONAHA.110.936393","volume":"122","author":"Z Mallat","year":"2010","unstructured":"Mallat, Z., Lambeau, G. & Tedgui, A. 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