{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,28]],"date-time":"2026-09-28T17:01:41Z","timestamp":1790614901358,"version":"4.1.0"},"reference-count":51,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"4","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["ATVB"],"published-print":{"date-parts":[[2013,4]]},"abstract":"<jats:sec>\n            <jats:title>Objective\u2014<\/jats:title>\n            <jats:p>Inactivating peroxisome proliferator-activated receptor-\u03b3 (PPAR\u03b3) mutations lead to a syndrome of familial partial lipodystrophy (FPLD3) associated with early-onset severe hypertension. PPAR\u03b3 can repress the vascular renin\u2013angiotensin system (RAS) and angiotensin II receptor 1 expression. We evaluated the relationships between PPAR\u03b3 inactivation and cellular RAS using FPLD3 patients\u2019 cells and human vascular smooth muscle cells expressing mutant or wild-type PPAR\u03b3.<\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Approach and Results\u2014<\/jats:title>\n            <jats:p>\n              We identified 2 novel\n              <jats:italic>PPAR<\/jats:italic>\n              G mutations, R165T and L339X, located in the DNA and ligand-binding domains of PPAR\u03b3, respectively in 4 patients from 2 FPLD3 families. In cultured skin fibroblasts and peripheral blood mononuclear cells from the 4 patients and healthy controls, we compared markers of RAS activation, oxidative stress, and inflammation, and tested the effect of modulators of PPAR\u03b3 and angiotensin II receptor 1. We studied the impact of the 2 mutations on the transcriptional activity of PPAR\u03b3 and on the vascular RAS in transfected human vascular smooth muscle cells. Systemic RAS was not altered in patients. However, RAS markers were overexpressed in patients\u2019 fibroblasts and peripheral blood mononuclear cells, as in vascular cells expressing mutant PPAR\u03b3. Angiotensin II\u2013mediated mitogen-activated protein kinase activity increased in patients\u2019 fibroblasts, consistent with RAS constitutive activation. Patients\u2019 cells also displayed oxidative stress and inflammation. PPAR\u03b3 activation and angiotensin II receptor 1 mRNA silencing reversed RAS overactivation, oxidative stress, and inflammation, arguing for a role of angiotensin II receptor 1 in these processes.\n            <\/jats:p>\n          <\/jats:sec>\n          <jats:sec>\n            <jats:title>Conclusions\u2014<\/jats:title>\n            <jats:p>\n              Two novel FPLD3-linked\n              <jats:italic>PPAR<\/jats:italic>\n              G mutations are associated with a defective transrepression of cellular RAS leading to cellular dysfunction, which might contribute to the specific FPLD3-linked severe hypertension.\n            <\/jats:p>\n          <\/jats:sec>","DOI":"10.1161\/atvbaha.112.300962","type":"journal-article","created":{"date-parts":[[2013,2,8]],"date-time":"2013-02-08T09:00:21Z","timestamp":1360314021000},"page":"829-838","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":62,"title":["Peroxisome Proliferator-Activated Receptor-\u03b3 Mutations Responsible for Lipodystrophy With Severe Hypertension Activate the Cellular Renin\u2013Angiotensin System"],"prefix":"10.1161","volume":"33","author":[{"given":"Martine","family":"Auclair","sequence":"first","affiliation":[{"name":"From INSERM UMRS938, Centre de Recherche Saint Antoine, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); UPMC Univ Paris 06, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (M.A., C.V., F.B., E.C., O.L., J.C., M.C-D.); AP-HP, H\u00f4pital Tenon, Service de Biochimie et Hormonologie, Paris, France (C.V., J.C.); AP-HP, H\u00f4pital Saint-Antoine, Service de Cardiologie, Paris, France (F.B.); AP-HP, H\u00f4pital H\u00f4tel-Dieu, Service de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Corinne","family":"Vigouroux","sequence":"additional","affiliation":[{"name":"From INSERM UMRS938, Centre de Recherche Saint Antoine, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); UPMC Univ Paris 06, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (M.A., C.V., F.B., E.C., O.L., J.C., M.C-D.); AP-HP, H\u00f4pital Tenon, Service de Biochimie et Hormonologie, Paris, France (C.V., J.C.); AP-HP, H\u00f4pital Saint-Antoine, Service de Cardiologie, Paris, France (F.B.); AP-HP, H\u00f4pital H\u00f4tel-Dieu, Service de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franck","family":"Boccara","sequence":"additional","affiliation":[{"name":"From INSERM UMRS938, Centre de Recherche Saint Antoine, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); UPMC Univ Paris 06, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (M.A., C.V., F.B., E.C., O.L., J.C., M.C-D.); AP-HP, H\u00f4pital Tenon, Service de Biochimie et Hormonologie, Paris, France (C.V., J.C.); AP-HP, H\u00f4pital Saint-Antoine, Service de Cardiologie, Paris, France (F.B.); AP-HP, H\u00f4pital H\u00f4tel-Dieu, Service de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Emilie","family":"Capel","sequence":"additional","affiliation":[{"name":"From INSERM UMRS938, Centre de Recherche Saint Antoine, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); UPMC Univ Paris 06, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (M.A., C.V., F.B., E.C., O.L., J.C., M.C-D.); AP-HP, H\u00f4pital Tenon, Service de Biochimie et Hormonologie, Paris, France (C.V., J.C.); AP-HP, H\u00f4pital Saint-Antoine, Service de Cardiologie, Paris, France (F.B.); AP-HP, H\u00f4pital H\u00f4tel-Dieu, Service de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Catherine","family":"Vigeral","sequence":"additional","affiliation":[{"name":"From INSERM UMRS938, Centre de Recherche Saint Antoine, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); UPMC Univ Paris 06, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (M.A., C.V., F.B., E.C., O.L., J.C., M.C-D.); AP-HP, H\u00f4pital Tenon, Service de Biochimie et Hormonologie, Paris, France (C.V., J.C.); AP-HP, H\u00f4pital Saint-Antoine, Service de Cardiologie, Paris, France (F.B.); AP-HP, H\u00f4pital H\u00f4tel-Dieu, Service de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruno","family":"Guerci","sequence":"additional","affiliation":[{"name":"From INSERM UMRS938, Centre de Recherche Saint Antoine, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); UPMC Univ Paris 06, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (M.A., C.V., F.B., E.C., O.L., J.C., M.C-D.); AP-HP, H\u00f4pital Tenon, Service de Biochimie et Hormonologie, Paris, France (C.V., J.C.); AP-HP, H\u00f4pital Saint-Antoine, Service de Cardiologie, Paris, France (F.B.); AP-HP, H\u00f4pital H\u00f4tel-Dieu, Service de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Olivier","family":"Lascols","sequence":"additional","affiliation":[{"name":"From INSERM UMRS938, Centre de Recherche Saint Antoine, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); UPMC Univ Paris 06, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (M.A., C.V., F.B., E.C., O.L., J.C., M.C-D.); AP-HP, H\u00f4pital Tenon, Service de Biochimie et Hormonologie, Paris, France (C.V., J.C.); AP-HP, H\u00f4pital Saint-Antoine, Service de Cardiologie, Paris, France (F.B.); AP-HP, H\u00f4pital H\u00f4tel-Dieu, Service de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jacqueline","family":"Capeau","sequence":"additional","affiliation":[{"name":"From INSERM UMRS938, Centre de Recherche Saint Antoine, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); UPMC Univ Paris 06, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (M.A., C.V., F.B., E.C., O.L., J.C., M.C-D.); AP-HP, H\u00f4pital Tenon, Service de Biochimie et Hormonologie, Paris, France (C.V., J.C.); AP-HP, H\u00f4pital Saint-Antoine, Service de Cardiologie, Paris, France (F.B.); AP-HP, H\u00f4pital H\u00f4tel-Dieu, Service de..."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Martine","family":"Caron-Debarle","sequence":"additional","affiliation":[{"name":"From INSERM UMRS938, Centre de Recherche Saint Antoine, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); UPMC Univ Paris 06, Paris, France (M.A., C.V., F.B, E.C, O.L, J.C, M.C-D.); ICAN, Institute of Cardiometabolism and Nutrition, Paris, France (M.A., C.V., F.B., E.C., O.L., J.C., M.C-D.); AP-HP, H\u00f4pital Tenon, Service de Biochimie et Hormonologie, Paris, France (C.V., J.C.); AP-HP, H\u00f4pital Saint-Antoine, Service de Cardiologie, Paris, France (F.B.); AP-HP, H\u00f4pital H\u00f4tel-Dieu, Service de..."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_4_2_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.biochem.77.061307.091829"},{"key":"e_1_3_4_3_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2007.03.006"},{"key":"e_1_3_4_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2007.12.008"},{"key":"e_1_3_4_5_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.101.11.1311"},{"key":"e_1_3_4_6_2","doi-asserted-by":"publisher","DOI":"10.1146\/annurev.pharmtox.46.120604.141247"},{"key":"e_1_3_4_7_2","doi-asserted-by":"publisher","DOI":"10.1111\/j.1365-2362.2008.02022.x"},{"key":"e_1_3_4_8_2","doi-asserted-by":"publisher","DOI":"10.1155\/2008\/285842"},{"key":"e_1_3_4_9_2","doi-asserted-by":"publisher","DOI":"10.1038\/nature03988"},{"key":"e_1_3_4_10_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tcm.2007.12.001"},{"key":"e_1_3_4_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/CIRCRESAHA.107.164384"},{"key":"e_1_3_4_12_2","doi-asserted-by":"publisher","DOI":"10.1038\/47254"},{"key":"e_1_3_4_13_2","doi-asserted-by":"publisher","DOI":"10.2337\/diabetes.52.4.910"},{"key":"e_1_3_4_14_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI28003"},{"key":"e_1_3_4_15_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2007-2356"},{"key":"e_1_3_4_16_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.tem.2009.04.005"},{"key":"e_1_3_4_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.109.144170"},{"key":"e_1_3_4_18_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJMra041811"},{"key":"e_1_3_4_19_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200420964"},{"key":"e_1_3_4_20_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M407539200"},{"key":"e_1_3_4_21_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.107.103648"},{"key":"e_1_3_4_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.109.184234"},{"key":"e_1_3_4_23_2","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0909657106"},{"key":"e_1_3_4_24_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M109.087718"},{"key":"e_1_3_4_25_2","doi-asserted-by":"publisher","DOI":"10.1210\/endo.142.7.8272"},{"key":"e_1_3_4_26_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.102.15.1834"},{"key":"e_1_3_4_27_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF03344010"},{"key":"e_1_3_4_28_2","doi-asserted-by":"publisher","DOI":"10.1152\/ajpregu.00507.2004"},{"key":"e_1_3_4_29_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.hyp.0000255576.16089.b9"},{"key":"e_1_3_4_30_2","doi-asserted-by":"publisher","DOI":"10.1155\/2009\/507141"},{"key":"e_1_3_4_31_2","doi-asserted-by":"publisher","DOI":"10.3851\/IMP1533"},{"key":"e_1_3_4_32_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.molmed.2010.03.002"},{"key":"e_1_3_4_33_2","doi-asserted-by":"publisher","DOI":"10.1042\/CS20120089"},{"key":"e_1_3_4_34_2","doi-asserted-by":"publisher","DOI":"10.1161\/hypertensionaha.110.168872"},{"key":"e_1_3_4_35_2","doi-asserted-by":"publisher","DOI":"10.1038\/hr.2009.5"},{"key":"e_1_3_4_36_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cmet.2006.09.003"},{"key":"e_1_3_4_37_2","doi-asserted-by":"publisher","DOI":"10.1007\/s00125-011-2142-4"},{"key":"e_1_3_4_38_2","doi-asserted-by":"publisher","DOI":"10.1210\/jc.2005-2624"},{"key":"e_1_3_4_39_2","doi-asserted-by":"publisher","DOI":"10.1186\/1471-2350-7-3"},{"key":"e_1_3_4_40_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbadis.2010.01.012"},{"key":"e_1_3_4_41_2","doi-asserted-by":"publisher","DOI":"10.1210\/en.2003-1271"},{"key":"e_1_3_4_42_2","doi-asserted-by":"publisher","DOI":"10.1097\/01.hjh.0000220402.53869.72"},{"key":"e_1_3_4_43_2","doi-asserted-by":"publisher","DOI":"10.4070\/kcj.2009.39.5.180"},{"key":"e_1_3_4_44_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.cardiores.2006.07.014"},{"key":"e_1_3_4_45_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvbaha.111.244962"},{"key":"e_1_3_4_46_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.R109.025031"},{"key":"e_1_3_4_47_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.str.0000138784.68159.a5"},{"key":"e_1_3_4_48_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.0000127122.22685.0A"},{"key":"e_1_3_4_49_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.bbalip.2007.02.013"},{"key":"e_1_3_4_50_2","doi-asserted-by":"publisher","DOI":"10.1016\/j.peptides.2011.09.010"},{"key":"e_1_3_4_51_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.cir.0000127955.36250.65"},{"key":"e_1_3_4_52_2","doi-asserted-by":"publisher","DOI":"10.1042\/BJ20100749"}],"container-title":["Arteriosclerosis, Thrombosis, and Vascular Biology"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/ATVBAHA.112.300962","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T22:47:05Z","timestamp":1715554025000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/ATVBAHA.112.300962"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2013,4]]},"references-count":51,"journal-issue":{"issue":"4","published-print":{"date-parts":[[2013,4]]}},"alternative-id":["10.1161\/ATVBAHA.112.300962"],"URL":"https:\/\/doi.org\/10.1161\/atvbaha.112.300962","relation":{},"ISSN":["1079-5642","1524-4636"],"issn-type":[{"value":"1079-5642","type":"print"},{"value":"1524-4636","type":"electronic"}],"subject":[],"published":{"date-parts":[[2013,4]]},"assertion":[{"value":"2012-03-27","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2012-12-30","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2013-02-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}