{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,3]],"date-time":"2026-09-03T03:08:58Z","timestamp":1788404938887,"version":"build-2803163510"},"reference-count":68,"publisher":"Oxford University Press (OUP)","issue":"13","license":[{"start":{"date-parts":[[2025,8,25]],"date-time":"2025-08-25T00:00:00Z","timestamp":1756080000000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100014389","name":"Amarin Pharma Inc.","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100014389","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100031637","name":"Elucida Research LLC","doi-asserted-by":"publisher","id":[{"id":"10.13039\/100031637","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2025,10,28]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Elevated lipoprotein(a) [Lp(a)] levels increase cardiovascular (CV) risk. Lp(a) contains oxidized phospholipids that may promote lipid oxidation more than other lipoproteins. The highly unsaturated omega-3 fatty acid eicosapentaenoic acid (EPA) has multiple double bonds that can trap free radicals in resonance structures. Purified ethyl-EPA reduced CV events in high-risk patients with elevated Lp(a) despite Lp(a)-associated risk elevation. Since Lp(a) is enriched in oxidized lipids, we hypothesized that Lp(a)-enriched plasma undergoes more rapid oxidation than other apolipoprotein B (ApoB)-containing particles and that EPA limits oxidation of Lp(a)-enriched plasma more effectively than less-unsaturated fatty acids or other lipid-lowering treatments. This property could limit the cellular stress responses in endothelial cells (ECs).<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Lp(a) was enriched to &amp;gt;50% total ApoB content to resemble an Lp(a)-associated \u2018high-risk\u2019 phenotype and compared with matching levels of small-dense LDL (sdLDL) and very-low-density lipoprotein by isopycnic centrifugation. Samples were then incubated with EPA (50\u2005\u00b5M) or equivolume vehicle at 37\u00b0C for 30\u2005min. Oxidation was initiated with copper sulfate and monitored by malondialdehyde formation. We also subjected EPA to oxidation before measuring its antioxidant activity when compared with other long chain, less saturated fatty acids and lipid-lowering agents. Human umbilical vein ECs (HUVECs) were incubated with Lp(a)-enriched plasma following oxidation in the absence and presence of EPA. Cell lysate samples were then analysed by global liquid chromatography-mass spectroscopy (LC\/MS)\u2013based proteomics for significant changes in protein expression (&amp;gt;1-fold). Lp(a)-enriched plasma contained the highest baseline oxidized lipid (P &amp;lt; 0.05) and underwent the most rapid oxidation. EPA, but neither the less-unsaturated fatty acids nor lipid agents attenuated oxidation of each fraction through 4\u2005h (P &amp;lt; 0.01). Oxidized EPA had diminished antioxidant capacity corresponding to the extent of oxidation. Attenuation of Lp(a) oxidation with EPA also mitigated pro-inflammatory and cellular stress response changes in protein expression.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusions<\/jats:title>\n                    <jats:p>Lp(a)-enriched plasma underwent more rapid oxidation than other ApoB-containing lipoproteins and promoted inflammatory changes in EC protein expression, a process attenuated by EPA. This action may contribute to reduced CV risk by EPA in those with elevated Lp(a) levels.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/cvr\/cvaf144","type":"journal-article","created":{"date-parts":[[2025,8,22]],"date-time":"2025-08-22T11:38:40Z","timestamp":1755862720000},"page":"2014-2026","source":"Crossref","is-referenced-by-count":5,"title":["Eicosapentaenoic acid limits the more rapid oxidation of lipoprotein(a) compared with other apolipoprotein B particles"],"prefix":"10.1093","volume":"121","author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-0913-2865","authenticated-orcid":false,"given":"Samuel C R","family":"Sherratt","sequence":"first","affiliation":[{"name":"Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai , 1 Gustave L. Levy Pl, New York, NY 10029 ,","place":["USA"]},{"name":"Elucida Research , 100 Cummings Center, Suite 135L, Beverly, MA 01915 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1502-502X","authenticated-orcid":false,"given":"Peter","family":"Libby","sequence":"additional","affiliation":[{"name":"Department of Medicine, Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School , 75 Francis St, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7059-4794","authenticated-orcid":false,"given":"Richard L","family":"Dunbar","sequence":"additional","affiliation":[{"name":"Amarin Pharma, Inc. , 440 Route 22 East, Suite 300, Bridgewater, NJ 08807 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-1278-6245","authenticated-orcid":false,"given":"Deepak L","family":"Bhatt","sequence":"additional","affiliation":[{"name":"Mount Sinai Fuster Heart Hospital, Icahn School of Medicine at Mount Sinai , 1 Gustave L. Levy Pl, New York, NY 10029 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5483-1852","authenticated-orcid":false,"given":"R Preston","family":"Mason","sequence":"additional","affiliation":[{"name":"Elucida Research , 100 Cummings Center, Suite 135L, Beverly, MA 01915 ,","place":["USA"]},{"name":"Department of Medicine, Cardiovascular Division, Brigham and Women\u2019s Hospital, Harvard Medical School , 75 Francis St, Boston, MA 02115 ,","place":["USA"]}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"286","published-online":{"date-parts":[[2025,8,25]]},"reference":[{"key":"2025102811283952600_cvaf144-B1","doi-asserted-by":"crossref","first-page":"760","DOI":"10.1001\/jamacardio.2022.0987","article-title":"Lipoprotein(a) and its significance in cardiovascular disease: a review","volume":"7","author":"Duarte Lau","year":"2022","journal-title":"JAMA 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