{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,5,1]],"date-time":"2026-05-01T06:20:46Z","timestamp":1777616446104,"version":"3.51.4"},"reference-count":33,"publisher":"Oxford University Press (OUP)","issue":"6","license":[{"start":{"date-parts":[[2026,2,2]],"date-time":"2026-02-02T00:00:00Z","timestamp":1769990400000},"content-version":"vor","delay-in-days":6097,"URL":"https:\/\/creativecommons.org\/licenses\/by-nc\/3.0\/"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":[],"published-print":{"date-parts":[[2009,6,1]]},"abstract":"<jats:title>Abstract<\/jats:title>\n                  <jats:sec>\n                    <jats:title>Aims<\/jats:title>\n                    <jats:p>Humans with inactivating mutations in peroxisomal proliferators activated receptor gamma (PPAR\u03b3) typically develop a complex metabolic syndrome characterized by insulin resistance, diabetes, lipodystrophy, hypertension, and dyslipidaemia which is likely to increase their cardiovascular risk. Despite evidence that the activation of PPAR\u03b3 may prevent cardiac fibrosis and hypertrophy, recent evidence has suggested that pharmacological activation of PPAR\u03b3 causes increased cardiovascular mortality. In this study, we investigated the effects of defective PPAR\u03b3 function on the development of cardiac fibrosis and hypertrophy in a murine model carrying a human dominant-negative mutation in PPAR\u03b3.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods and results<\/jats:title>\n                    <jats:p>Mice with a dominant-negative point mutation in PPAR\u03b3 (P465L) and their wild-type (WT) littermates were treated with either subcutaneous angiotensin II (AngII) infusion or saline for 2 weeks. Heterozygous P465L and WT mice developed a similar increase in systolic blood pressure, but the mutant mice developed significantly more severe cardiac fibrosis to AngII that correlated with increased expression of profibrotic genes. Both groups similarly increased the heart weight to body weight ratio compared with saline-treated controls. There were no differences in fibrosis between saline-treated WT and P465L mice.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Conclusion<\/jats:title>\n                    <jats:p>These results show synergistic pathogenic effects between the presence of defective PPAR\u03b3 and AngII-induced hypertension and suggest that patients with PPAR\u03b3 mutation and hypertension may need more aggressive therapeutic measures to reduce the risk of accelerated cardiac fibrosis.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.1093\/eurjhf\/hfp048","type":"journal-article","created":{"date-parts":[[2009,4,25]],"date-time":"2009-04-25T20:12:44Z","timestamp":1240690364000},"page":"533-541","source":"Crossref","is-referenced-by-count":33,"title":["Defective Peroxisomal Proliferators Activated Receptor Gamma Activity Due to Dominant-Negative Mutation Synergizes with Hypertension to Accelerate Cardiac Fibrosis in Mice"],"prefix":"10.1093","volume":"11","author":[{"given":"Adrienn","family":"Kis","sequence":"first","affiliation":[{"name":"Metabolic Research Laboratories, Level 4, Institute of Metabolic Sciences , Box 289, Addenbrooke\u2019s Hospital, Cambridge, CB2 0QQ ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Colin","family":"Murdoch","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, King\u2019s College London British Heart Foundation Centre of Research Excellence , 125 Coldharbour Lane, London, SE5 9NU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Min","family":"Zhang","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, King\u2019s College London British Heart Foundation Centre of Research Excellence , 125 Coldharbour Lane, London, SE5 9NU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Anjana","family":"Siva","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, King\u2019s College London British Heart Foundation Centre of Research Excellence , 125 Coldharbour Lane, London, SE5 9NU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Sergio","family":"Rodriguez-Cuenca","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Level 4, Institute of Metabolic Sciences , Box 289, Addenbrooke\u2019s Hospital, Cambridge, CB2 0QQ ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Stefania","family":"Carobbio","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Level 4, Institute of Metabolic Sciences , Box 289, Addenbrooke\u2019s Hospital, Cambridge, CB2 0QQ 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L.","family":"Gray","sequence":"additional","affiliation":[{"name":"Northern Medical Program, University of Northern British Columbia, 3333 University Way, Prince George BC , Prince George, BC, V2N 479 ,","place":["Canada"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Ajay M.","family":"Shah","sequence":"additional","affiliation":[{"name":"Cardiovascular Division, King\u2019s College London British Heart Foundation Centre of Research Excellence , 125 Coldharbour Lane, London, SE5 9NU ,","place":["UK"]}],"role":[{"role":"author","vocabulary":"crossref"}]},{"given":"Antonio","family":"Vidal-Puig","sequence":"additional","affiliation":[{"name":"Metabolic Research Laboratories, Level 4, Institute of Metabolic Sciences , Box 289, Addenbrooke\u2019s Hospital, Cambridge, CB2 0QQ 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