{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T13:04:35Z","timestamp":1784898275785,"version":"3.55.0"},"reference-count":52,"publisher":"American Society for Clinical Investigation","issue":"14","license":[{"start":{"date-parts":[[2026,7,22]],"date-time":"2026-07-22T00:00:00Z","timestamp":1784678400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/100000002","name":"National Institutes of Health","doi-asserted-by":"crossref","award":["R01HL159171,UM1HG008853"],"award-info":[{"award-number":["R01HL159171,UM1HG008853"]}],"id":[{"id":"10.13039\/100000002","id-type":"DOI","asserted-by":"crossref"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2026,7,22]]},"abstract":"<jats:p>\n                    A single-nucleotide missense polymorphism (rs1800449, R158Q) in the propeptide domain of lysyl oxidase (LOX-PP) is associated with increased risk of coronary artery disease (CAD) independent of changes in plasma lipid levels. Although the enzymatic function of LOX has an essential role for the cross-linking of extracellular matrix proteins in connective tissues, whether and how LOX-PP R158Q contributes to the development of atherosclerosis has not been clearly established. Here, hypercholesterolemia was induced in mice that were WT or homozygous for the LOX-PP R158Q polymorphism by adeno-associated virus-8\u2013mediated overexpression of\n                    <jats:italic>Pcsk9<\/jats:italic>\n                    followed by high-fat diet feeding for 16 weeks. We found that the R158Q polymorphism promoted atherosclerosis and induced proliferation of macrophages and vascular smooth muscle cells without altering LOX enzymatic activity. Using single-cell RNA sequencing, we found the transcriptional program of atherosclerotic plaques from mice harboring R158Q was strongly enriched for proliferation- and calcification-related genes in a regionally distinct manner. Together, these results establish an enzymatically independent proatherogenic role for the LOX-PP and suggest its potential as a novel therapeutic target.\n                  <\/jats:p>","DOI":"10.1172\/jci.insight.201535","type":"journal-article","created":{"date-parts":[[2026,7,21]],"date-time":"2026-07-21T18:01:12Z","timestamp":1784656872000},"source":"Crossref","is-referenced-by-count":0,"title":["A loss-of-function polymorphism in the propeptide of lysyl oxidase exacerbates atherosclerosis"],"prefix":"10.1172","volume":"11","author":[{"given":"In-Hyuk","family":"Jung","sequence":"first","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Junedh M.","family":"Amrute","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofia E.","family":"Luna","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ryan E.","family":"Wagoner","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Arturo","family":"Alisio","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Paul C.","family":"Lee","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kendall H.","family":"Burks","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joohee","family":"Oh","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hannah C.","family":"Plunkett Paletta","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Chul Joo","family":"Kang","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-4963-8211","authenticated-orcid":true,"given":"Nathan O.","family":"Stitziel","sequence":"additional","affiliation":[{"name":"Center for Cardiovascular Research, Division of Cardiology, Department of Medicine, and"},{"name":"Department of Genetics, Washington University School of Medicine, St. Louis, Missouri, USA."},{"name":"John Cochran Veterans Affairs Medical Center, St. Louis, Missouri, USA."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"232","published-online":{"date-parts":[[2026,7,22]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","DOI":"10.1016\/j.bpj.2014.05.014"},{"key":"B2","doi-asserted-by":"publisher","DOI":"10.1016\/S0945-053X(98)90012-9"},{"key":"B3","doi-asserted-by":"publisher","DOI":"10.1038\/nrc3319"},{"key":"B4","doi-asserted-by":"publisher","DOI":"10.1038\/bjc.2013.535"},{"key":"B5","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-04-1543"},{"key":"B6","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-08-4818"},{"key":"B7","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-06-3867"},{"key":"B8","doi-asserted-by":"publisher","DOI":"10.1152\/ajpheart.00335.2010"},{"key":"B9","doi-asserted-by":"publisher","DOI":"10.1358\/dnp.2008.21.4.1213351"},{"key":"B10","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/cvn102"},{"key":"B11","doi-asserted-by":"publisher","DOI":"10.3390\/cells8121483"},{"key":"B12","doi-asserted-by":"publisher","DOI":"10.1093\/carcin\/bgy045"},{"key":"B13","doi-asserted-by":"publisher","DOI":"10.1038\/ng.3914"},{"key":"B14","doi-asserted-by":"publisher","DOI":"10.1007\/s00418-012-0940-5"},{"key":"B15","doi-asserted-by":"publisher","DOI":"10.1369\/jhc.2009.954354"},{"key":"B16","doi-asserted-by":"publisher","DOI":"10.2144\/05381RV01"},{"key":"B17","doi-asserted-by":"publisher","DOI":"10.1161\/01.STR.0000223001.06264.af"},{"key":"B18","doi-asserted-by":"publisher","DOI":"10.1016\/S0891-5849(00)00227-6"},{"key":"B19","doi-asserted-by":"publisher","DOI":"10.1016\/0303-7207(95)96799-N"},{"issue":"3","key":"B20","first-page":"668","article-title":"Active proliferation of different cell types, including lymphocytes, in human atherosclerotic plaques","volume":"147","author":"Rekhter","year":"1995","journal-title":"Am J Pathol"},{"key":"B21","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbrc.2007.11.116"},{"key":"B22","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M803413200"},{"key":"B23","doi-asserted-by":"publisher","DOI":"10.1093\/jb\/mvi159"},{"key":"B24","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-4644(19991001)75:1<177::AID-JCB18>3.0.CO;2-W"},{"key":"B25","doi-asserted-by":"publisher","DOI":"10.1002\/1097-4644(20001215)79:4<576::AID-JCB60>3.0.CO;2-A"},{"key":"B26","doi-asserted-by":"publisher","DOI":"10.1002\/jcb.10181"},{"key":"B27","doi-asserted-by":"publisher","DOI":"10.1016\/j.biopha.2023.115469"},{"key":"B28","doi-asserted-by":"publisher","DOI":"10.1038\/s41591-019-0512-5"},{"key":"B29","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.120.318049"},{"key":"B30","doi-asserted-by":"publisher","DOI":"10.1161\/ATVBAHA.107.141069"},{"key":"B31","doi-asserted-by":"publisher","DOI":"10.1038\/sj.onc.1203551"},{"key":"B32","doi-asserted-by":"publisher","DOI":"10.1172\/JCI0215650"},{"key":"B33","doi-asserted-by":"publisher","DOI":"10.1158\/0008-5472.CAN-10-0894"},{"key":"B34","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2018.05.009"},{"key":"B35","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.109.213702"},{"key":"B36","doi-asserted-by":"publisher","DOI":"10.1091\/mbc.e09-03-0227"},{"key":"B37","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.118.311227"},{"key":"B38","doi-asserted-by":"publisher","DOI":"10.1146\/annurev-med-041717-085853"},{"key":"B39","doi-asserted-by":"publisher","DOI":"10.1038\/453840a"},{"key":"B40","doi-asserted-by":"publisher","DOI":"10.1096\/fj.201700653R"},{"key":"B41","doi-asserted-by":"publisher","DOI":"10.1160\/TH14-01-0024"},{"key":"B42","doi-asserted-by":"publisher","DOI":"10.1038\/s41598-018-31312-w"},{"key":"B43","doi-asserted-by":"publisher","DOI":"10.1002\/oby.22074"},{"key":"B44","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(00)00694-9"},{"key":"B45","doi-asserted-by":"publisher","DOI":"10.1038\/ncb1909"},{"key":"B46","doi-asserted-by":"publisher","DOI":"10.1186\/s12964-022-00993-2"},{"key":"B47","doi-asserted-by":"publisher","DOI":"10.33549\/physiolres.933779"},{"key":"B48","doi-asserted-by":"publisher","DOI":"10.1371\/journal.pone.0105579"},{"key":"B49","doi-asserted-by":"publisher","DOI":"10.1089\/dna.2010.1098"},{"key":"B50","doi-asserted-by":"publisher","DOI":"10.1177\/147323001204000310"},{"key":"B51","doi-asserted-by":"publisher","DOI":"10.3390\/ijms24119407"},{"key":"B52","doi-asserted-by":"publisher","DOI":"10.3390\/ijerph13070635"}],"container-title":["JCI Insight"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/insight.jci.org\/articles\/view\/201535\/files\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2026,7,24]],"date-time":"2026-07-24T12:34:32Z","timestamp":1784896472000},"score":1,"resource":{"primary":{"URL":"https:\/\/insight.jci.org\/articles\/view\/201535"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2026,7,22]]},"references-count":52,"journal-issue":{"issue":"14","published-online":{"date-parts":[[2026,7,22]]},"published-print":{"date-parts":[[2026,7,22]]}},"alternative-id":["10.1172\/jci.insight.201535"],"URL":"https:\/\/doi.org\/10.1172\/jci.insight.201535","relation":{},"ISSN":["2379-3708"],"issn-type":[{"value":"2379-3708","type":"electronic"}],"subject":[],"published":{"date-parts":[[2026,7,22]]},"article-number":"e201535"}}