{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,18]],"date-time":"2026-08-18T01:53:44Z","timestamp":1787018024290,"version":"build-2736575974"},"reference-count":47,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2025,5]]},"abstract":"\n BACKGROUND:<\/jats:title>\n \n FFAR4 (free fatty acid receptor 4) has emerged as a target for preventing cardiovascular disease through its ability to control macrophage inflammation and foam cell formation. Previous studies have shown that FFAR4 activation can protect against the accumulation of arterial plaque buildup in atherosclerotic animal models. The goal of our study is to test the hypothesis that FFAR4 deficiency will increase atherosclerotic plaque development in\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice.\n <\/jats:p>\n <\/jats:sec>\n \n METHODS:<\/jats:title>\n \n Male and female\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n \/Ffar4<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice and their\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n controls were fed a Western diet for 8 or 16 weeks to assess early and advanced atherosclerotic lesions, respectively. At the end of each study, atherosclerotic plaque severity was determined by analyzing the aortic sinus lesion area of the heart and the en face lesion area of the aortic arch.\n <\/jats:p>\n <\/jats:sec>\n \n RESULTS:<\/jats:title>\n \n Following 8 weeks of Western diet feeding, lesions from\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n \/Ffar4<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n male and female mice had 33% and 22% decreases, respectively, in the aortic sinus lesion area with no changes in the aortic arch lesion area. After 16 weeks of Western diet feeding, the lesions showed no changes in the area or volume of the aortic sinus between\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n \/Ffar4<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice and\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n controls. However, male\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n \/Ffar4<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice had a 27% increase in the plaque lesion area in the aortic arch compared with\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n controls. Despite similar sizes of lesions in the aortic sinus,\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n \/Ffar4<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n mice had larger necrotic cores compared with the\n apoE<\/jats:italic>\n \n \u2212\/\u2212<\/jats:italic>\n <\/jats:sup>\n control mice. In fact, male and female mice had 43% and 37% increases in the necrotic lesion area, respectively.\n <\/jats:p>\n <\/jats:sec>\n \n CONCLUSIONS:<\/jats:title>\n These data suggest a novel role for FFAR4 in reducing necrotic core lesion formation and support a protective role for FFAR4 in stabilizing atherosclerotic plaques.<\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/atvbaha.124.322371","type":"journal-article","created":{"date-parts":[[2025,3,6]],"date-time":"2025-03-06T05:00:48Z","timestamp":1741237248000},"page":"675-682","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":3,"title":["FFAR4 Deficiency Increases Necrotic Cores in Advanced Lesions of ApoE\n \u2212\/\u2212<\/sup>\n Mice\u2014Brief Report"],"prefix":"10.1161","volume":"45","author":[{"ORCID":"https:\/\/orcid.org\/0000-0001-5865-6000","authenticated-orcid":true,"given":"Gage M.","family":"Stuttgen","sequence":"first","affiliation":[{"name":"Department of Biochemistry (G.M.S., J.M.B., M.L., S.N.H., D.S.), Medical College of Wisconsin, Milwaukee."},{"name":"Cardiovascular Center (G.M.S., J.M.B., R.P., D.S.), Medical College of Wisconsin, Milwaukee."},{"name":"Center for Immunology (G.M.S., D.S.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jordan M.","family":"Bobek","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (G.M.S., J.M.B., M.L., S.N.H., D.S.), Medical College of Wisconsin, Milwaukee."},{"name":"Cardiovascular Center (G.M.S., J.M.B., R.P., D.S.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Renee","family":"Penoske","sequence":"additional","affiliation":[{"name":"Cardiovascular Center (G.M.S., J.M.B., R.P., D.S.), Medical College of Wisconsin, Milwaukee."},{"name":"Department of Medicine, Division of Endocrinology and Molecular Medicine (R.P., D.S.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-8194-8543","authenticated-orcid":true,"given":"Caris","family":"Wadding-Lee","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, OH (C.W.-L., A.P.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michael","family":"Lam","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (G.M.S., J.M.B., M.L., S.N.H., D.S.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-6564-091X","authenticated-orcid":true,"given":"Shelby N.","family":"Hader","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (G.M.S., J.M.B., M.L., S.N.H., D.S.), Medical College of Wisconsin, Milwaukee."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-0835-620X","authenticated-orcid":true,"suffix":"III","given":"A. Phillip","family":"Owens","sequence":"additional","affiliation":[{"name":"Department of Internal Medicine, Division of Cardiovascular Health and Disease, University of Cincinnati, OH (C.W.-L., A.P.O.)."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0001-5210-6497","authenticated-orcid":true,"given":"Daisy","family":"Sahoo","sequence":"additional","affiliation":[{"name":"Department of Biochemistry (G.M.S., J.M.B., M.L., S.N.H., D.S.), Medical College of Wisconsin, Milwaukee."},{"name":"Cardiovascular Center (G.M.S., J.M.B., R.P., D.S.), Medical College of Wisconsin, Milwaukee."},{"name":"Center for Immunology (G.M.S., D.S.), Medical College of Wisconsin, Milwaukee."},{"name":"Department of Medicine, Division of Endocrinology and Molecular Medicine (R.P., D.S.), Medical College of Wisconsin, Milwaukee."},{"name":"H4930 Health Research Center (D.S.), Medical College of Wisconsin, 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