{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,12]],"date-time":"2026-09-12T05:00:26Z","timestamp":1789189226798,"version":"build-2803163510"},"reference-count":32,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"2","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2001,2]]},"abstract":"<jats:p>\n            Aldosterone  is implicated in cardiac hypertrophy and fibrosis. We  tested the role of the mineralocorticoid receptor in a model of  angiotensin II\u2013induced cardiac injury. We administered  spironolactone (SPIRO; 20 mg \u00b7  kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7 d\n            <jats:sup>\u22121<\/jats:sup>\n            ), valsartan (VAL; 10  mg \u00b7 kg\n            <jats:sup>\u22121<\/jats:sup>\n            \u00b7  d\n            <jats:sup>\u22121<\/jats:sup>\n            ), or vehicle to rats double transgenic  for the human renin and angiotensinogen genes (dTGR). We  investigated basic fibroblast growth factor (bFGF),  platelet-derived growth factor, transforming growth  factor-\u03b2\n            <jats:sub>1<\/jats:sub>\n            , and the transcription factors AP-1  and nuclear factor (NF)-\u03baB. We used immunohistochemistry,  electrophoretic mobility shift assays, and TaqMan RT-PCR. Untreated  dTGR developed hypertension, cardiac hypertrophy,  vasculopathy, and fibrosis with a 50% mortality rates at 7 weeks.  SPIRO and VAL prevented death and reversed cardiac  hypertrophy, while only VAL normalized blood pressure. Both  drugs prevented vasculopathy. bFGF was markedly upregulated in dTGR,  whereas platelet-derived growth factor-B and transforming growth  factor-\u03b2\n            <jats:sub>1<\/jats:sub>\n            were little changed. VAL and SPIRO  suppressed this upregulation. Both AP-1 and NF-\u03baB were  activated in dTGR compared with controls. VAL and SPIRO reduced  both transcription factors and reduced bFGF, collagen I, fibronectin,  and laminin in the interstitium. These findings show that  aldosterone promotes hypertrophy, cardiac  remodeling, and fibrosis, independent of blood pressure. The effects  involve AP-1, NF-\u03baB, and bFGF. Mineralocorticoid receptor blockade  downregulates these effectors and reduces angiotensin  II\u2013induced cardiac damage.\n          <\/jats:p>","DOI":"10.1161\/01.hyp.37.2.787","type":"journal-article","created":{"date-parts":[[2012,6,12]],"date-time":"2012-06-12T00:25:31Z","timestamp":1339460731000},"page":"787-793","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":151,"title":["Mineralocorticoid Receptor Affects AP-1 and Nuclear Factor-\u03baB Activation in Angiotensin II\u2013Induced Cardiac Injury"],"prefix":"10.1161","volume":"37","author":[{"given":"Anette","family":"Fiebeler","sequence":"first","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Folke","family":"Schmidt","sequence":"additional","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominik N.","family":"Mu\u0308ller","sequence":"additional","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Joon-Keun","family":"Park","sequence":"additional","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ralf","family":"Dechend","sequence":"additional","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Markus","family":"Bieringer","sequence":"additional","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Erdenechimeg","family":"Shagdarsuren","sequence":"additional","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Volker","family":"Breu","sequence":"additional","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Hermann","family":"Haller","sequence":"additional","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Friedrich C.","family":"Luft","sequence":"additional","affiliation":[{"name":"From the Franz Volhard Clinic and Max Delbru\u0308ck Center, Medical  Faculty of the Charite\u0301, Humboldt University of Berlin, and Department  of Medicine-Nephrology, Hoffmann La Roche Inc, Basel, Schwitzerland; and  Hannover Medical School, University of Hannover, Germany."}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_3_2_2_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(90)90475-G"},{"key":"e_1_3_2_3_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.99.20.2694"},{"key":"e_1_3_2_4_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00973.x"},{"key":"e_1_3_2_5_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(18)99065-4"},{"key":"e_1_3_2_6_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.67.6.1700933"},{"key":"e_1_3_2_7_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0022-2828(95)90359-3"},{"key":"e_1_3_2_8_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00962.x"},{"key":"e_1_3_2_9_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.33.4.981"},{"key":"e_1_3_2_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.33.1.212"},{"key":"e_1_3_2_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.35.1.193"},{"key":"e_1_3_2_12_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9440(10)64523-3"},{"key":"e_1_3_2_13_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.9.4883"},{"key":"e_1_3_2_14_2","doi-asserted-by":"crossref","unstructured":"Brilla CG Rupp H Funck R Maisch B. The renin-angiotensin-aldosterone system and myocardial collagen matrix remodelling in congestive heart failure. Eur Heart J. 1995;16(suppl O):107\u2013109.","DOI":"10.1093\/eurheartj\/16.suppl_O.107"},{"key":"e_1_3_2_15_2","first-page":"404","volume":"122","year":"1993","unstructured":"Sun Y, Weber KT. Angiotensin II and aldosterone receptor binding in rat heart and kidney: response to chronic angiotensin II or aldosterone administration. J Lab Clin Med. 1993;122:404\u2013411.","journal-title":"J Lab Clin Med"},{"key":"e_1_3_2_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.33.1.232"},{"key":"e_1_3_2_17_2","doi-asserted-by":"publisher","DOI":"10.1161\/atvb.17.6.1152"},{"key":"e_1_3_2_18_2","doi-asserted-by":"publisher","DOI":"10.1681\/ASN.V104814"},{"key":"e_1_3_2_19_2","doi-asserted-by":"publisher","DOI":"10.1046\/j.1523-1755.2000.00304.x"},{"key":"e_1_3_2_20_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.36.3.330"},{"key":"e_1_3_2_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0898-6568(97)00043-0"},{"key":"e_1_3_2_22_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0021-9258(17)42228-9"},{"key":"e_1_3_2_23_2","doi-asserted-by":"publisher","DOI":"10.1038\/nm0298-201"},{"key":"e_1_3_2_24_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI7315"},{"key":"e_1_3_2_25_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.94.10.2566"},{"key":"e_1_3_2_26_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI118106"},{"key":"e_1_3_2_27_2","doi-asserted-by":"publisher","DOI":"10.1161\/res.85.7.565"},{"key":"e_1_3_2_28_2","doi-asserted-by":"publisher","DOI":"10.1083\/jcb.111.5.2149"},{"key":"e_1_3_2_29_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1998.0902"},{"key":"e_1_3_2_30_2","doi-asserted-by":"publisher","DOI":"10.1006\/bbrc.1996.0418"},{"key":"e_1_3_2_31_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.273.41.26487"},{"key":"e_1_3_2_32_2","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.271.6.3272"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/01.HYP.37.2.787","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,12]],"date-time":"2024-05-12T18:43:24Z","timestamp":1715539404000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/01.HYP.37.2.787"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2001,2]]},"references-count":32,"journal-issue":{"issue":"2","published-print":{"date-parts":[[2001,2]]}},"alternative-id":["10.1161\/01.HYP.37.2.787"],"URL":"https:\/\/doi.org\/10.1161\/01.hyp.37.2.787","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,2]]},"assertion":[{"value":"2000-10-25","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2000-12-14","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-02-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}