{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,27]],"date-time":"2026-10-27T13:34:55Z","timestamp":1793108095023,"version":"4.5.0"},"reference-count":22,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","license":[{"start":{"date-parts":[[2021,5,5]],"date-time":"2021-05-05T00:00:00Z","timestamp":1620172800000},"content-version":"tdm","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2021,5,5]]},"abstract":"<jats:sec>\n            <jats:title>Objective:<\/jats:title>\n            <jats:p>The mechanism by which evinacumab, a fully human monoclonal antibody directed against ANGPTL3 (angiopoietin-like 3 protein) lowers plasma LDL (low-density lipoprotein) cholesterol levels in patients with homozygous familial hypercholesterolemia is unknown. We investigated apoB (apolipoprotein B) containing lipoprotein kinetic parameters in patients with homozygous familial hypercholesterolemia, before and after treatment with evinacumab.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results:<\/jats:title>\n            <jats:p>\n              Four patients with homozygous familial hypercholesterolemia underwent apoB kinetic analyses in 2 centers as part of a substudy of a trial evaluating the efficacy and safety of evinacumab in patients with homozygous familial hypercholesterolemia. The enrichment of apoB with the stable isotope (5,5,5-\n              <jats:sup>2<\/jats:sup>\n              H\n              <jats:sub>3<\/jats:sub>\n              )-Leucine was measured in VLDL (very LDL), IDL (intermediate-density lipoprotein), and LDL at different time points before and after intravenous administration of 15 mg\/kg evinacumab. Evinacumab lowered LDL-cholesterol by 59\u00b12% and increased IDL apoB and LDL apoB fractional catabolic rate in all 4 homozygous familial hypercholesterolemia subjects, by 616\u00b1504% and 113\u00b114%, respectively. VLDL-apoB production rate decreased in 2 of the 4 subjects.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions:<\/jats:title>\n            <jats:p>In this small study, ANGPTL3 inhibition with evinacumab is associated with an increase in the fractional catabolic rate of IDL apoB and LDL apoB, suggesting that evinacumab lowers LDL-cholesterol predominantly by increasing apoB-containing lipoprotein clearance from the circulation. Additional studies are needed to unravel which factors are determinants in this biological pathway.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Registration:<\/jats:title>\n            <jats:p>\n              URL:\n              <jats:ext-link xmlns:xlink=\"http:\/\/www.w3.org\/1999\/xlink\" ext-link-type=\"uri\" xlink:href=\"https:\/\/www.clinicaltrials.gov\">https:\/\/www.clinicaltrials.gov<\/jats:ext-link>\n              ; Unique identifier: NCT04722068.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.120.315204","type":"journal-article","created":{"date-parts":[[2021,3,11]],"date-time":"2021-03-11T10:02:05Z","timestamp":1615456925000},"page":"1753-1759","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":108,"title":["ANGPTL3 Inhibition With Evinacumab Results in Faster Clearance of IDL and LDL apoB in Patients With Homozygous Familial Hypercholesterolemia\u2014Brief Report"],"prefix":"10.1161","volume":"41","clinical-trial-number":[{"clinical-trial-number":"nct04722068","registry":"10.18810\/clinical-trials-gov"}],"author":[{"ORCID":"https:\/\/orcid.org\/0000-0002-8043-951X","authenticated-orcid":true,"given":"Laurens F.","family":"Reeskamp","sequence":"first","affiliation":[{"name":"Department of Vascular Medicine (L.F.R., G.K.H.), Amsterdam UMC, location AMC, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"John S.","family":"Millar","sequence":"additional","affiliation":[{"name":"Institute for Diabetes, Obesity, and Metabolism (J.S.M.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."},{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine (J.S.M., L.W., D.J.R., M.C.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Liya","family":"Wu","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine (J.S.M., L.W., D.J.R., M.C.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hans","family":"Jansen","sequence":"additional","affiliation":[{"name":"Department of Experimental Vascular Medicine (H.J.), Amsterdam UMC, location AMC, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-7277-3323","authenticated-orcid":true,"given":"Dewi","family":"van Harskamp","sequence":"additional","affiliation":[{"name":"Stable Isotope Research Laboratory, Endocrinology, Vrije Universiteit (D.v.H., H.S.), Amsterdam UMC, location AMC, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Henk","family":"Schierbeek","sequence":"additional","affiliation":[{"name":"Stable Isotope Research Laboratory, Endocrinology, Vrije Universiteit (D.v.H., H.S.), Amsterdam UMC, location AMC, University of Amsterdam, The Netherlands."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel A.","family":"Gipe","sequence":"additional","affiliation":[{"name":"Regeneron Pharmaceuticals, Inc, Tarrytown, NY (D.A.G.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-9245-9876","authenticated-orcid":true,"given":"Daniel J.","family":"Rader","sequence":"additional","affiliation":[{"name":"Division of Translational Medicine and Human Genetics, Department of Medicine (J.S.M., L.W., D.J.R., M.C.), Perelman School of Medicine, University of Pennsylvania, Philadelphia."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5412-5923","authenticated-orcid":true,"given":"Geesje M.","family":"Dallinga-Thie","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8145-1676","authenticated-orcid":true,"given":"G. 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