{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2025,12,30]],"date-time":"2025-12-30T08:48:06Z","timestamp":1767084486967,"version":"3.41.2"},"reference-count":55,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"15","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["JAHA"],"published-print":{"date-parts":[[2020,8,4]]},"abstract":"<jats:sec xml:lang=\"en\">\n            <jats:title>Background<\/jats:title>\n            <jats:p xml:lang=\"en\">Activated vascular cells produce submicron prothrombotic and proinflammatory microparticle vesicles. Atherosclerotic plaques contain high levels of microparticles. Plasma microparticle levels increase during acute coronary syndromes and the thrombotic consequences of plaque rupture likely involve macrophage\u2010derived microparticles (M\u03a6MPs). The activation pathways that promote M\u03a6MP production remain poorly defined. This study tested the hypothesis that signals implicated in atherogenesis also stimulate M\u03a6MP production.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Methods and Results<\/jats:title>\n            <jats:p xml:lang=\"en\">\n              We stimulated human primary M\u03a6s with proinflammatory cytokines and atherogenic lipids, and measured M\u03a6MP production by flow cytometry. Oxidized low\u2010density lipoprotein (oxLDL; 25\u00a0\u00b5g\/mL) induced M\u03a6MP production in a concentration\u2010dependent manner (293% increase;\n              <jats:italic>P<\/jats:italic>\n              &lt;0.001), and these oxLDL M\u03a6MP stimulatory effects were mediated by CD36. OxLDL stimulation increased M\u03a6MP tissue factor content by 78% (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05), and oxLDL\u2010induced M\u03a6MP production correlated with activation of caspase 3\/7 signaling pathways. Salvionolic acid B, a CD36 inhibitor and a CD36 inhibitor antibody reduced oxLDL\u2010induced M\u03a6MP by 67% and 60%, respectively. Caspase 3\/7 inhibition reduced M\u03a6MP release by 52% (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01) and caspase 3\/7 activation increased M\u03a6MP production by 208% (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01). Mevastatin pretreatment (10\u00a0\u00b5M) decreased oxLDL\u2010induced caspase 3\/7 activation and attenuated oxLDL\u2010stimulated M\u03a6MP production and tissue factor content by 60% (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.01) and 43% (\n              <jats:italic>P<\/jats:italic>\n              &lt;0.05), respectively.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec xml:lang=\"en\">\n            <jats:title>Conclusions<\/jats:title>\n            <jats:p xml:lang=\"en\">OxLDL induces the production of prothrombotic microparticles in macrophages. This process depends on caspases 3 and 7 and CD36 and is inhibited by mevastatin pretreatment. These findings link atherogenic signaling pathways, inflammation, and plaque thrombogenicity and identify a novel potential mechanism for antithrombotic effects of statins independent of LDL lowering.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/jaha.120.015878","type":"journal-article","created":{"date-parts":[[2020,7,31]],"date-time":"2020-07-31T09:12:23Z","timestamp":1596186743000},"update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":14,"title":["Oxidized Low\u2010Density Lipoprotein Induces Macrophage Production of Prothrombotic Microparticles"],"prefix":"10.1161","volume":"9","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-2279-1945","authenticated-orcid":false,"given":"Julio F.","family":"Marchini","sequence":"first","affiliation":[{"name":"Cardiovascular Division Department of Medicine Brigham and Women\u2019s HospitalHarvard Medical School Boston MA"},{"name":"Departamento de Cl\u00ednica M\u00e9dica Instituto 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