{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T03:02:04Z","timestamp":1787022124513,"version":"build-2736575974"},"reference-count":46,"publisher":"Public Library of Science (PLoS)","issue":"5","license":[{"start":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T00:00:00Z","timestamp":1683676800000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"name":"NIH","award":["R01 AG048366"],"award-info":[{"award-number":["R01 AG048366"]}]},{"DOI":"10.13039\/100000009","name":"Foundation for the National Institutes of Health","doi-asserted-by":"publisher","award":["R01 AG050238"],"award-info":[{"award-number":["R01 AG050238"]}],"id":[{"id":"10.13039\/100000009","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/100007496","name":"Biomedical Laboratory Research and Development, VA Office of Research and Development","doi-asserted-by":"publisher","award":["I01 BX004492"],"award-info":[{"award-number":["I01 BX004492"]}],"id":[{"id":"10.13039\/100007496","id-type":"DOI","asserted-by":"publisher"}]},{"name":"NIH","award":["R01 AG060395"],"award-info":[{"award-number":["R01 AG060395"]}]}],"content-domain":{"domain":["www.plosone.org"],"crossmark-restriction":false},"short-container-title":["PLoS ONE"],"abstract":"<jats:p>\n                    Atherosclerosis is the root cause of major cardiovascular diseases (CVD) such as myocardial infarction and stroke. ADP-ribosylation factor 6 (Arf6) is a ubiquitously expressed GTPase known to be involved in inflammation, vascular permeability and is sensitive to changes in shear stress. Here, using atheroprone,\n                    <jats:italic>ApoE<\/jats:italic>\n                    <jats:sup>\n                      <jats:italic>-\/-<\/jats:italic>\n                    <\/jats:sup>\n                    mice, with a single allele deletion of\n                    <jats:italic>Arf6<\/jats:italic>\n                    (HET) or wildtype\n                    <jats:italic>Arf6<\/jats:italic>\n                    (WT), we demonstrate that reduction in Arf6 attenuates atherosclerotic plaque burden and severity. We found that plaque burden in the descending aorta was lower in HET compared to WT mice (p\u02c20.001) after the consumption of an atherogenic Paigen diet for 5 weeks. Likewise, luminal occlusion, necrotic core size, plaque grade, elastic lamina breaks, and matrix deposition were lower in the aortic root atheromas of HET compared to WT mice (all p\u22640.05). We also induced advanced human-like complex atherosclerotic plaque in the left carotid artery using partial carotid ligation surgery and found that atheroma area, plaque grade, intimal necrosis, intraplaque hemorrhage, thrombosis, and calcification were lower in HET compared to WT mice (all p\u22640.04). Our findings suggest that the atheroprotection afforded by\n                    <jats:italic>Arf6<\/jats:italic>\n                    heterozygosity may result from reduced immune cell migration (all p\u22640.005) as well as endothelial and vascular smooth muscle cell proliferation (both p\u22640.001) but independent of changes in circulating lipids (all p\u22650.40). These findings demonstrate a critical role for Arf6 in the development and severity of atherosclerosis and suggest that Arf6 inhibition can be explored as a novel therapeutic strategy for the treatment of atherosclerotic CVD.\n                  <\/jats:p>","DOI":"10.1371\/journal.pone.0285253","type":"journal-article","created":{"date-parts":[[2023,5,10]],"date-time":"2023-05-10T14:15:14Z","timestamp":1683728114000},"page":"e0285253","update-policy":"https:\/\/doi.org\/10.1371\/journal.pone.corrections_policy","source":"Crossref","is-referenced-by-count":7,"title":["Heterozygosity for ADP-ribosylation factor 6 suppresses the burden and severity of atherosclerosis"],"prefix":"10.1371","volume":"18","author":[{"given":"Venkateswara R.","family":"Gogulamudi","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8263-0628","authenticated-orcid":true,"given":"Md Torikul","family":"Islam","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jessica R.","family":"Durrant","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-8362-7412","authenticated-orcid":true,"given":"Adelola O.","family":"Adeyemo","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Daniel W.","family":"Trott","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mi Ho","family":"Hyuhn","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Weiquan","family":"Zhu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anthony J.","family":"Donato","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ashley E.","family":"Walker","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-2138-1450","authenticated-orcid":true,"given":"Lisa A.","family":"Lesniewski","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"340","published-online":{"date-parts":[[2023,5,10]]},"reference":[{"issue":"12","key":"pone.0285253.ref001","doi-asserted-by":"crossref","first-page":"2295","DOI":"10.1113\/JP279774","article-title":"Impact of statins on vascular smooth muscle cells and relevance to atherosclerosis","volume":"598","author":"T. 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