Please use this identifier to cite or link to this item:
https://hdl.handle.net/1959.11/31277
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DC Field | Value | Language |
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dc.contributor.author | Burke, Amy C | en |
dc.contributor.author | Telford, Dawn E | en |
dc.contributor.author | Sutherland, Brian G | en |
dc.contributor.author | Edwards, Jane Y | en |
dc.contributor.author | Sawyez, Cynthia G | en |
dc.contributor.author | Barrett, P Hugh R | en |
dc.contributor.author | Newton, Roger S | en |
dc.contributor.author | Pickering, J Geoffrey | en |
dc.contributor.author | Huff, Murray W | en |
dc.date.accessioned | 2021-08-11T04:11:48Z | - |
dc.date.available | 2021-08-11T04:11:48Z | - |
dc.date.issued | 2018-05 | - |
dc.identifier.citation | Arteriosclerosis, Thrombosis, and Vascular Biology, 38(5), p. 1178-1190 | en |
dc.identifier.issn | 1524-4636 | en |
dc.identifier.issn | 1079-5642 | en |
dc.identifier.uri | https://hdl.handle.net/1959.11/31277 | - |
dc.description.abstract | <p><i><b>Objective</b></i>—Bempedoic acid (BemA; ETC-1002) is a novel drug that targets hepatic ATP-citrate lyase to reduce cholesterol biosynthesis. In phase 2 studies, BemA lowers elevated low-density lipoprotein cholesterol (LDL-C) in hypercholesterolemic patients. In the present study, we tested the ability of BemA to decrease plasma cholesterol and LDL-C and attenuate atherosclerosis in a large animal model of familial hypercholesterolemia.</p><p> <i><b>Approach and Results</b></i>—Gene targeting has been used to generate Yucatan miniature pigs heterozygous (<i>LDLR<sup>+/−</sup></i>) or homozygous (<i>LDLR<sup>−/−</sup></i>) for LDL receptor deficiency (ExeGen). <i>LDLR<sup>+/−</sup></i> and <i>LDLR<sup>−/−</i></sup></sup></i> pigs were fed a high-fat, cholesterol-containing diet (34% kcal fat; 0.2% cholesterol) and orally administered placebo or BemA for 160 days. In <i>LDLR<sup>+/−</sup></i> pigs, compared with placebo, BemA decreased plasma cholesterol and LDL-C up to 40% and 61%, respectively. In <i>LDLR<sup>−/−</sup></i> pigs, in which plasma cholesterol and LDL-C were 5-fold higher than in <i>LDLR<sup>+/−</sup></i> pigs, BemA decreased plasma cholesterol and LDL-C up to 27% and 29%, respectively. Plasma levels of triglycerides and high-density lipoprotein cholesterol, fasting glucose and insulin, and liver lipids were unaffected by treatment in either genotype. In the aorta of <i>LDLR<sup>+/−</sup></i> pigs, BemA robustly attenuated en face raised lesion area (−58%) and left anterior descending coronary artery cross-sectional lesion area (−40%). In <i>LDLR<sup>−/−</sup></i> pigs, in which lesions were substantially more advanced, BemA decreased aortic lesion area (−47%) and left anterior descending coronary artery lesion area (−48%).</p><p> <i><b>Conclusions</b></i>—In a large animal model of <i>LDLR</i> deficiency and atherosclerosis, long-term treatment with BemA reduces LDL-C and attenuates the development of aortic and coronary atherosclerosis in both <i>LDLR<sup>+/−</sup></i> and <i>LDLR<sup>−/−</sup></i> miniature pigs.</p> | en |
dc.language | en | en |
dc.publisher | Lippincott Williams & Wilkins | en |
dc.relation.ispartof | Arteriosclerosis, Thrombosis, and Vascular Biology | en |
dc.title | Bempedoic Acid Lowers Low-Density Lipoprotein Cholesterol and Attenuates Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient (LDLR+/− and LDLR−/−) Yucatan Miniature Pigs | en |
dc.type | Journal Article | en |
dc.identifier.doi | 10.1161/ATVBAHA.117.310676 | en |
dc.identifier.pmid | 29449335 | en |
dcterms.accessRights | Gold | en |
local.contributor.firstname | Amy C | en |
local.contributor.firstname | Dawn E | en |
local.contributor.firstname | Brian G | en |
local.contributor.firstname | Jane Y | en |
local.contributor.firstname | Cynthia G | en |
local.contributor.firstname | P Hugh R | en |
local.contributor.firstname | Roger S | en |
local.contributor.firstname | J Geoffrey | en |
local.contributor.firstname | Murray W | en |
local.profile.school | Faculty of Medicine and Health | en |
local.profile.email | pbarret6@une.edu.au | en |
local.output.category | C1 | en |
local.record.place | au | en |
local.record.institution | University of New England | en |
local.publisher.place | United States of America | en |
local.format.startpage | 1178 | en |
local.format.endpage | 1190 | en |
local.identifier.scopusid | 85053133306 | en |
local.peerreviewed | Yes | en |
local.identifier.volume | 38 | en |
local.identifier.issue | 5 | en |
local.access.fulltext | Yes | en |
local.contributor.lastname | Burke | en |
local.contributor.lastname | Telford | en |
local.contributor.lastname | Sutherland | en |
local.contributor.lastname | Edwards | en |
local.contributor.lastname | Sawyez | en |
local.contributor.lastname | Barrett | en |
local.contributor.lastname | Newton | en |
local.contributor.lastname | Pickering | en |
local.contributor.lastname | Huff | en |
dc.identifier.staff | une-id:pbarret6 | en |
local.profile.orcid | 0000-0003-3223-6125 | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.profile.role | author | en |
local.identifier.unepublicationid | une:1959.11/31277 | en |
local.date.onlineversion | 2018-02-15 | - |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
dc.identifier.academiclevel | Academic | en |
local.title.maintitle | Bempedoic Acid Lowers Low-Density Lipoprotein Cholesterol and Attenuates Atherosclerosis in Low-Density Lipoprotein Receptor–Deficient (LDLR+/− and LDLR−/−) Yucatan Miniature Pigs | en |
local.relation.fundingsourcenote | This work was supported by grants to M.W. Huff from Esperion Therapeutics Inc, Ann Arbor, MI, and the Canadian Institutes for Health Research (MOP-126045). A.C. Burke was supported by a Doctoral Award from the Canadian Diabetes Association (DS-3-14-4588-AB). | en |
local.output.categorydescription | C1 Refereed Article in a Scholarly Journal | en |
local.search.author | Burke, Amy C | en |
local.search.author | Telford, Dawn E | en |
local.search.author | Sutherland, Brian G | en |
local.search.author | Edwards, Jane Y | en |
local.search.author | Sawyez, Cynthia G | en |
local.search.author | Barrett, P Hugh R | en |
local.search.author | Newton, Roger S | en |
local.search.author | Pickering, J Geoffrey | en |
local.search.author | Huff, Murray W | en |
local.uneassociation | No | en |
local.atsiresearch | No | en |
local.sensitive.cultural | No | en |
local.year.available | 2018 | en |
local.year.published | 2018 | en |
local.fileurl.closedpublished | https://rune.une.edu.au/web/retrieve/d7f29c2a-285e-4e02-8457-9f9cb53d7f13 | en |
local.subject.for2020 | 320101 Cardiology (incl. cardiovascular diseases) | en |
local.subject.for2020 | 320803 Systems physiology | en |
local.subject.seo2020 | 200105 Treatment of human diseases and conditions | en |
dc.notification.token | 2146cd68-dc7a-4fc6-a468-860e7471c014 | en |
Appears in Collections: | Journal Article |
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