{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,30]],"date-time":"2026-09-30T19:04:30Z","timestamp":1790795070096,"version":"4.1.0"},"reference-count":20,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2016,4]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>To determine effects of single ascending doses of MDCO-216 on high-density lipoprotein (HDL) subfractions in relation to changes in cholesterol efflux capacity in healthy volunteers and in patients with stable angina pectoris.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              Doses of 5- (in volunteers only), 10-, 20-, 30-, and 40-mg\/kg MDCO-216 were infused during 2 hours, and plasma and serum were collected during 30 days. Plasma levels of HDL subfractions were assessed by 2-dimensional gel electrophoresis, immunoblotting, and image analysis. Lipoprotein particle concentrations and sizes were also assessed by proton nuclear magnetic resonance (\n              <jats:sup>1<\/jats:sup>\n              H-NMR). There was a rapid dose-dependent increase of total apolipoprotein A-I (apoA-I) in pre-\u03b21, \u03b1-1, and \u03b1-2 HDL levels and decrease in \u03b1-3 and \u03b1-4 HDL. Using a selective antibody apoA-IMilano was detected in the large \u03b1-1 and \u03b1-2 HDL on all doses and at each time point. ApoA-IMilano was also detected at the \u03b1-4 position but only at high doses.\n              <jats:sup>1<\/jats:sup>\n              H-NMR analysis similarly showed a rapid and dose-dependent shift from small- to large-sized HDL particles. The increase of basal and ATP-binding cassette transporter A1\u2013mediated efflux capacities reported previously correlated strongly and independently with the increase in pre-\u03b21-HDL and \u03b1-1 HDL, but not with that in \u03b1-2 HDL.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>On infusion, MDCO-216 rapidly eliminates small HDL and leads to formation of \u03b1-1 and \u03b1-2 HDL containing both wild-type apoA-I and apoA-IMilano. In this process, endogenous apoA-I is liberated appearing as pre-\u03b21-HDL. In addition to pre-\u03b21-HDL, the newly formed \u03b1-1 HDL particle containing apoA-I Milano may have a direct effect on cholesterol efflux capacity.<\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.115.307052","type":"journal-article","created":{"date-parts":[[2016,2,26]],"date-time":"2016-02-26T04:33:49Z","timestamp":1456461229000},"page":"736-742","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":38,"title":["High-Density Lipoprotein Subfractions and Cholesterol Efflux Capacities After Infusion of MDCO-216 (Apolipoprotein A-IMilano\/Palmitoyl-Oleoyl-Phosphatidylcholine) in Healthy Volunteers and Stable Coronary Artery Disease Patients"],"prefix":"10.1161","volume":"36","author":[{"given":"Herman J.","family":"Kempen","sequence":"first","affiliation":[{"name":"From The Medicines Company (Schweiz) GmbH, Z\u00fcrich, Switzerland (H.J.K., D.G.K., P.L.J.W.); Lipid Metabolism Laboratory, Tufts University, Boston, MA (B.F.A.); Center of Human Drug Research, Leiden, The Netherlands (M.M.); Liposcience, Laboratory Corporation of America Holdings, Raleigh, NC (E.J., J.O.); and The Medicines Company Inc, Parsippany, NJ (S.E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bela F.","family":"Asztalos","sequence":"additional","affiliation":[{"name":"From The Medicines Company (Schweiz) GmbH, Z\u00fcrich, Switzerland (H.J.K., D.G.K., P.L.J.W.); Lipid Metabolism Laboratory, Tufts University, Boston, MA (B.F.A.); Center of Human Drug Research, Leiden, The Netherlands (M.M.); Liposcience, Laboratory Corporation of America Holdings, Raleigh, NC (E.J., J.O.); and The Medicines Company Inc, Parsippany, NJ (S.E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Matthijs","family":"Moerland","sequence":"additional","affiliation":[{"name":"From The Medicines Company (Schweiz) GmbH, Z\u00fcrich, Switzerland (H.J.K., D.G.K., P.L.J.W.); Lipid Metabolism Laboratory, Tufts University, Boston, MA (B.F.A.); Center of Human Drug Research, Leiden, The Netherlands (M.M.); Liposcience, Laboratory Corporation of America Holdings, Raleigh, NC (E.J., J.O.); and The Medicines Company Inc, Parsippany, NJ (S.E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Elias","family":"Jeyarajah","sequence":"additional","affiliation":[{"name":"From The Medicines Company (Schweiz) GmbH, Z\u00fcrich, Switzerland (H.J.K., D.G.K., P.L.J.W.); Lipid Metabolism Laboratory, Tufts University, Boston, MA (B.F.A.); Center of Human Drug Research, Leiden, The Netherlands (M.M.); Liposcience, Laboratory Corporation of America Holdings, Raleigh, NC (E.J., J.O.); and The Medicines Company Inc, Parsippany, NJ (S.E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"James","family":"Otvos","sequence":"additional","affiliation":[{"name":"From The Medicines Company (Schweiz) GmbH, Z\u00fcrich, Switzerland (H.J.K., D.G.K., P.L.J.W.); Lipid Metabolism Laboratory, Tufts University, Boston, MA (B.F.A.); Center of Human Drug Research, Leiden, The Netherlands (M.M.); Liposcience, Laboratory Corporation of America Holdings, Raleigh, NC (E.J., J.O.); and The Medicines Company Inc, Parsippany, NJ (S.E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David G.","family":"Kallend","sequence":"additional","affiliation":[{"name":"From The Medicines Company (Schweiz) GmbH, Z\u00fcrich, Switzerland (H.J.K., D.G.K., P.L.J.W.); Lipid Metabolism Laboratory, Tufts University, Boston, MA (B.F.A.); Center of Human Drug Research, Leiden, The Netherlands (M.M.); Liposcience, Laboratory Corporation of America Holdings, Raleigh, NC (E.J., J.O.); and The Medicines Company Inc, Parsippany, NJ (S.E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"S. Eralp","family":"Bellibas","sequence":"additional","affiliation":[{"name":"From The Medicines Company (Schweiz) GmbH, Z\u00fcrich, Switzerland (H.J.K., D.G.K., P.L.J.W.); Lipid Metabolism Laboratory, Tufts University, Boston, MA (B.F.A.); Center of Human Drug Research, Leiden, The Netherlands (M.M.); Liposcience, Laboratory Corporation of America Holdings, Raleigh, NC (E.J., J.O.); and The Medicines Company Inc, Parsippany, NJ (S.E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Peter L.J.","family":"Wijngaard","sequence":"additional","affiliation":[{"name":"From The Medicines Company (Schweiz) GmbH, Z\u00fcrich, Switzerland (H.J.K., D.G.K., P.L.J.W.); Lipid Metabolism Laboratory, Tufts University, Boston, MA (B.F.A.); Center of Human Drug Research, Leiden, The Netherlands (M.M.); Liposcience, Laboratory Corporation of America Holdings, Raleigh, NC (E.J., J.O.); and The Medicines Company Inc, Parsippany, NJ (S.E.B.)."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9343(77)90874-9"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(90)90561-E"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(90)90562-F"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114722"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1126\/science.271.5248.518"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCULATIONAHA.104.475715"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI114558"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.91.20.9607"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.100.17.1816"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.15.1949"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1001\/jama.290.17.2292"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M033779"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1093\/ehjcvp\/pvv041"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1155\/2014\/923903"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1021\/bi970505a"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M041038"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1194\/jlr.M500187-JLR200"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1373\/clinchem.2009.139931"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.amjcard.2011.03.054"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.atherosclerosis.2009.07.038"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.115.307052","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T23:07:02Z","timestamp":1715555222000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.115.307052"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2016,4]]},"references-count":20,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2016,4]]}},"alternative-id":["10.1161\/ATVBAHA.115.307052"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.115.307052","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2016,4]]},"assertion":[{"value":"2015-12-16","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-12","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2016-02-25","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}