Scientific Sessions 2024  /  Novel Mechanisms Describing the Roles of Lipids in Cardiovascular Diseases  /  Dose-Dependent Inhibition of Lp(a) Oxidation by Eicosapentaenoic Acid (EPA) Compared to a Fibrate and Statin due to Lipid Interactions and Antioxidant Properties
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American Heart Association

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Final ID: MDP3

Dose-Dependent Inhibition of Lp(a) Oxidation by Eicosapentaenoic Acid (EPA) Compared to a Fibrate and Statin due to Lipid Interactions and Antioxidant Properties

Abstract Body (Do not enter title and authors here): Background: Elevated Lp(a) levels are an independent and causal risk factor for cardiovascular (CV) disease. Levels of oxidized Lp(a) were more predictive of CV events and endothelial dysfunction than non-oxidized forms in patients. The omega-3 fatty acid EPA reduced CV events in high-risk patients, including those with elevated Lp(a) (REDUCE-IT). EPA inhibits lipid oxidation due to scavenging activity and lipophilicity. We compared the effects of a pharmacologic concentration of EPA on oxidation rates for Lp(a) versus LDL compared to a fibrate and statin, along with lipid affinity.
Methods: Lp(a) was enriched to 66% of total ApoB-containing particles from patients with elevated levels by isopycnic centrifugation. Samples of Lp(a) and LDL (50 µg/ml) were incubated at 37°C for 30 min with EPA at various concentrations (10 – 100 µM) compared to equimolar fenofibric acid or rosuvastatin (10 µM). Samples then underwent copper sulfate-induced oxidation (20 µM) monitored by formation of malondialdehyde (MDA). Lipid affinity of each agent was measured by UV/Vis spectroscopy using lipid vesicles containing phosphatidylcholine and cholesterol at a 0.3:1 ratio. Drug concentrations in vesicles versus buffer were measured and compared to standard curves.
Results: Lp(a) enriched ApoB particles underwent time-dependent oxidation by 51-fold, peaking after 2 h (4.13 ± 0.10, p<0.001). EPA significantly inhibited Lp(a) oxidation in a dose and time-dependent manner; after 2 h, EPA inhibited oxidation from 31 to 69% (p<0.001) at 5 concentrations while fenofibric acid and rosuvastatin lacked antioxidant activity. Similar distinct antioxidant effects of EPA were observed in non-modified LDL. The antioxidant activity EPA correlated with higher lipid affinity that was significantly greater than fenofibric acid and rosuvastatin (p<0.001).
Conclusions: EPA inhibited oxidation of Lp(a) enriched plasma in a dose-dependent fashion due to potent scavenging mechanism and high lipid affinity. The fibrate or statin tested did not exert similar antioxidant effects. The potent antioxidant actions of EPA may contribute to reduced events in REDUCE-IT, including in subjects with elevated Lp(a).
  • Sherratt, Samuel  ( Mount Sinai Fuster Heart Hospital , New York , New York , United States )
  • Libby, Peter  ( BRIGHAM AND WOMENS HOSPITAL , Boston , Massachusetts , United States )
  • Bhatt, Deepak  ( Mount Sinai Fuster Heart Hospital , New York , New York , United States )
  • Mason, Preston  ( Brigham and Womens Hospital , Beverly , Massachusetts , United States )
    • Author Disclosures:
    Samuel Sherratt: DO have relevant financial relationships ; Employee:Elucida Research:Active (exists now) | Peter Libby: DO have relevant financial relationships ; Consultant:Amgen, Baim Institute, Beren Therapeutics, Esperion Therapeutics, Genentech, Kancera, Kowa Pharmaceuticals, Novo Nordisk, Novartis, and Sanofi-Regeneron:Active (exists now) ; Other (please indicate in the box next to the company name):Dr. Libby is on the Board of Directors of XBiotech, Inc. Dr. Libby has a financial interest in Xbiotech, a company developing therapeutic human antibodies, in TenSixteen Bio, a company targeting somatic mosaicism and clonal hematopoiesis of indeterminate potential (CHIP) to discover and develop novel therapeutics to treat age-related diseases, and in Soley Therapeutics, a biotechnology company that is combining artificial intelligence with molecular and cellular response detection for discovering and developing new drugs, currently focusing on cancer therapeutics. Dr. Libby’s interests were reviewed and are managed by Brigham and Women’s Hospital and Mass General Brigham in accordance with their conflict-of-interest policies.:Active (exists now) ; Other (please indicate in the box next to the company name):Dr. Libby’s laboratory has received research funding in the last 2 years from Novartis, Novo Nordisk and Genentech:Active (exists now) ; Advisor:AmAmgen, Caristo Diagnostics, CSL Behring, Elucid Bioimaging, Kancera, Kowa Pharmaceuticals, Olatec Therapeutics, Novartis, PlaqueTec, Polygon Therapeutics, TenSixteen Bio, Soley Thereapeutics, and XBiotech, Inc.:Active (exists now) | Deepak Bhatt: DO have relevant financial relationships ; Advisor:Angiowave, Bayer, Boehringer Ingelheim, CellProthera, Cereno Scientific, Elsevier Practice Update Cardiology, High Enroll, Janssen, Level Ex, McKinsey, Medscape Cardiology, Merck, MyoKardia, NirvaMed, Novo Nordisk, PhaseBio, PLx Pharma, Stasys:Active (exists now) ; Other (please indicate in the box next to the company name):Trustee: American College of Cardiology; Unfunded Research: FlowCo:Active (exists now) ; Other (please indicate in the box next to the company name):Site Co-Investigator: Abbott, Biotronik, Boston Scientific, CSI, Endotronix, St. Jude Medical (now Abbott), Philips, SpectraWAVE, Svelte, Vascular Solutions;:Active (exists now) ; Royalties/Patent Beneficiary:Royalties: Elsevier (Editor, Braunwald’s Heart Disease):Active (exists now) ; Researcher:Abbott, Acesion Pharma, Afimmune, Aker Biomarine, Alnylam, Amarin, Amgen, AstraZeneca, Bayer, Beren, Boehringer Ingelheim, Boston Scientific, Bristol-Myers Squibb, Cardax, CellProthera, Cereno Scientific, Chiesi, CinCor, Cleerly, CSL Behring, Eisai, Ethicon, Faraday Pharmaceuticals, Ferring Pharmaceuticals, Forest Laboratories, Fractyl, Garmin, HLS Therapeutics, Idorsia, Ironwood, Ischemix, Janssen, Javelin, Lexicon, Lilly, Medtronic, Merck, Moderna, MyoKardia, NirvaMed, Novartis, Novo Nordisk, Otsuka, Owkin, Pfizer, PhaseBio, PLx Pharma, Recardio, Regeneron, Reid Hoffman Foundation, Roche, Sanofi, Stasys, Synaptic, The Medicines Company, Youngene, 89Bio;:Active (exists now) ; Royalties/Patent Beneficiary:Patent: Sotagliflozin (named on a patent for sotagliflozin assigned to Brigham and Women's Hospital who assigned to Lexicon; neither I nor Brigham and Women's Hospital receive any income from this patent);:Active (exists now) ; Other (please indicate in the box next to the company name):Honoraria: Level Ex, Medtelligence/ReachMD (CME steering committees), MJH Life Sciences, Oakstone CME (Course Director, Comprehensive Review of Interventional Cardiology), Piper Sandler, Population Health Research Institute (for the COMPASS operations committee, publications committee, steering committee, and USA national co-leader, funded by Bayer), WebMD (CME steering committees), Wiley (steering committee);:Active (exists now) ; Other (please indicate in the box next to the company name):Honoraria: American College of Cardiology (Senior Associate Editor, Clinical Trials and News, ACC.org; Chair, ACC Accreditation Oversight Committee), Arnold and Porter law firm (work related to Sanofi/Bristol-Myers Squibb clopidogrel litigation), Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute; RE-DUAL PCI clinical trial steering committee funded by Boehringer Ingelheim; AEGIS-II executive committee funded by CSL Behring), Belvoir Publications (Editor in Chief, Harvard Heart Letter), Canadian Medical and Surgical Knowledge Translation Research Group (clinical trial steering committees), CSL Behring (AHA lecture), Cowen and Company, Duke Clinical Research Institute (clinical trial steering committees, including for the PRONOUNCE trial, funded by Ferring Pharmaceuticals), HMP Global (Editor in Chief, Journal of Invasive Cardiology), Journal of the American College of Cardiology (Guest Editor; Associate Editor), K2P (Co-Chair, interdisciplinary curriculum):Active (exists now) ; Other (please indicate in the box next to the company name):Data Monitoring Committees: Acesion Pharma, Assistance Publique-Hôpitaux de Paris, Baim Institute for Clinical Research (formerly Harvard Clinical Research Institute, for the PORTICO trial, funded by St. Jude Medical, now Abbott), Boston Scientific (Chair, PEITHO trial), Cleveland Clinic, Contego Medical (Chair, PERFORMANCE 2), Duke Clinical Research Institute, Mayo Clinic, Mount Sinai School of Medicine (for the ENVISAGE trial, funded by Daiichi Sankyo; for the ABILITY-DM trial, funded by Concept Medical; for ALLAY-HF, funded by Alleviant Medical), Novartis, Population Health Research Institute; Rutgers University (for the NIH-funded MINT Trial);:Active (exists now) ; Consultant:Broadview Ventures, GlaxoSmithKline, Hims, SFJ, Youngene:Active (exists now) ; Other (please indicate in the box next to the company name):Board of Directors: American Heart Association New York City, Angiowave (stock options), Bristol Myers Squibb (stock), DRS.LINQ (stock options), High Enroll (stock);:Active (exists now) | Preston Mason: DO have relevant financial relationships ; Research Funding (PI or named investigator):Amarin:Active (exists now) ; Consultant:Esperion:Past (completed) ; Consultant:Boehringer Ingelheim:Active (exists now) ; Research Funding (PI or named investigator):Lexicon:Past (completed) ; Research Funding (PI or named investigator):Viatris:Active (exists now)
Meeting Info:

Scientific Sessions 2024

2024

Chicago, Illinois

Session Info:

Novel Mechanisms Describing the Roles of Lipids in Cardiovascular Diseases

Saturday, 11/16/2024 , 09:30AM - 10:55AM

Moderated Digital Poster Session

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