{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2024,5,13]],"date-time":"2024-05-13T09:53:48Z","timestamp":1715594028448},"reference-count":40,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"6","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2012,6]]},"abstract":"\n Objective\u2014<\/jats:title>\n \n The dominant-negative mutation,\n P467L<\/jats:italic>\n , in peroxisome proliferator\u2013activated receptor-\u03b3 (PPAR\u03b3) affects adipose tissue distribution, insulin sensitivity, and blood pressure in heterozygous humans. We hypothesized that the equivalent mutation, PPAR\u03b3-\n P465L<\/jats:italic>\n , in mice will worsen atherosclerosis.\n <\/jats:p>\n <\/jats:sec>\n \n Methods and Results\u2014<\/jats:title>\n \n Apolipoprotein E\u2013null mice with and without PPAR\u03b3-\n P465L<\/jats:italic>\n mutation were bred in 129S6 inbred genetic background. Mild hypertension and lipodystrophy of PPAR\u03b3-\n P465L<\/jats:italic>\n persisted in the apolipoprotein E\u2013null background. Glucose homeostasis was normal, but plasma adiponectin was significantly lower and resistin was higher in PPAR\u03b3-\n P465L<\/jats:italic>\n mice. Plasma cholesterol and lipoprotein distribution were not different, but plasma triglycerides tended to be reduced. Surprisingly, there were no overall changes in the atherosclerotic plaque size or composition. PPAR\u03b3-\n P465L<\/jats:italic>\n macrophages had a small decrease in CD36 mRNA and a small yet significant reduction in very-low-density lipoprotein uptake in culture. In unloaded apolipoprotein E\u2013null macrophages with PPAR\u03b3-\n P465L<\/jats:italic>\n , cholesterol uptake was reduced whereas apolipoprotein AI\u2013mediated efflux was increased. However, when cells were cholesterol loaded in the presence of acetylated low-density lipoprotein, no genotype difference in uptake or efflux was apparent. A reduction of vascular cell adhesion molecule-1 expression in aorta suggests a relatively antiatherogenic vascular environment in mice with PPAR\u03b3-\n P465L<\/jats:italic>\n .\n <\/jats:p>\n <\/jats:sec>\n \n Conclusion\u2014<\/jats:title>\n \n Small, competing pro- and antiatherogenic effects of PPAR\u03b3-\n P465L<\/jats:italic>\n mutation result in unchanged plaque development in apolipoprotein E\u2013deficient mice.\n <\/jats:p>\n <\/jats:sec>","DOI":"10.1161\/atvbaha.112.248682","type":"journal-article","created":{"date-parts":[[2012,4,27]],"date-time":"2012-04-27T05:56:26Z","timestamp":1335506186000},"page":"1436-1444","update-policy":"http:\/\/dx.doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":5,"title":["Pro- and Antiatherogenic Effects of a Dominant-Negative P465L Mutation of Peroxisome Proliferator\u2013Activated Receptor-\u03b3 in Apolipoprotein E\u2013Null Mic"],"prefix":"10.1161","volume":"32","author":[{"given":"Avani A.","family":"Pendse","sequence":"first","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Lance A.","family":"Johnson","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Hyung-Suk","family":"Kim","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Marcus","family":"McNair","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"C. Taylor","family":"Nipp","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Carolyn","family":"Wilhelm","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Nobuyo","family":"Maeda","sequence":"additional","affiliation":[{"name":"From the Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, Chapel Hill, NC."}],"role":[{"role":"author","vocabulary":"crossref"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.atv.0000111245.75752.c6"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.21.3.372"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI10370"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.ATV.21.3.365"},{"key":"e_1_3_4_6_2","first-page":"64","article-title":"PPAR gamma: an essential role in metabolic control.","volume":"11","author":"Fajas L","year":"2001","unstructured":"Fajas L, Debril MB, Auwerx J. 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