{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,4]],"date-time":"2026-10-04T13:20:38Z","timestamp":1791120038651,"version":"4.1.0"},"reference-count":31,"publisher":"National Academy of Sciences","issue":"10","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2002,5,14]]},"abstract":"<jats:p>Cardiac failure is a common feature in the evolution of cardiac disease. Among the determinants of cardiac failure, the renin\u2013angiotensin\u2013aldosterone system has a central role, and antagonism of the mineralocorticoid receptor (MR) has been proposed as a therapeutic strategy. In this study, we questioned the role of the MR, not of aldosterone, on heart function, using an inducible and cardiac-specific transgenic mouse model. We have generated a conditional knock-down model by expressing solely in the heart an antisense mRNA directed against the murine MR, a transcription factor with unknown targets in cardiomyocytes. Within 2\u20133 mo, mice developed severe heart failure and cardiac fibrosis in the absence of hypertension or chronic hyperaldosteronism. Moreover, cardiac failure and fibrosis were fully reversible when MR antisense mRNA expression was subsequently suppressed.<\/jats:p>","DOI":"10.1073\/pnas.102673599","type":"journal-article","created":{"date-parts":[[2002,7,26]],"date-time":"2002-07-26T10:46:49Z","timestamp":1027680409000},"page":"7160-7165","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":85,"title":["Reversible cardiac fibrosis and heart failure induced by conditional expression of an antisense mRNA of the mineralocorticoid receptor in cardiomyocytes"],"prefix":"10.1073","volume":"99","author":[{"given":"Ahmed T.","family":"Beggah","sequence":"first","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Escoubet","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stefania","family":"Puttini","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Stephane","family":"Cailmail","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Vanessa","family":"Delage","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Antoine","family":"Ouvrard-Pascaud","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Bocchi","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Michel","family":"Peuchmaur","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Claude","family":"Delcayre","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nicolette","family":"Farman","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Frederic","family":"Jaisser","sequence":"additional","affiliation":[{"name":"Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U478 and U426, H\u00f4pital Bichat\u2013Claude Bernard, AP-HP, Federative Institute of Research 02, 75870 Paris, France; Institut National de la Sant\u00e9 et de la Recherche M\u00e9dicale U127, Federative Institute of Research 06, 75010 Paris, France; and Pathology Unit and EA 3102, R. Debre Hospital, 75019 Paris, France"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2002,5,7]]},"reference":[{"key":"e_1_3_4_1_2","doi-asserted-by":"crossref","first-page":"215","DOI":"10.1152\/physrev.1999.79.1.215","volume":"79","author":"Swynghedauw B","year":"1999","unstructured":"B Swynghedauw Physiol Rev 79, 215\u2013262 (1999).","journal-title":"Physiol Rev"},{"key":"e_1_3_4_2_2","doi-asserted-by":"crossref","first-page":"7","DOI":"10.1016\/S0008-6363(99)00088-7","volume":"43","author":"Delcayre C","year":"1999","unstructured":"C Delcayre, J S Silvestre Cardiovasc Res 43, 7\u201312 (1999).","journal-title":"Cardiovasc Res"},{"key":"e_1_3_4_3_2","doi-asserted-by":"crossref","first-page":"709","DOI":"10.1056\/NEJM199909023411001","volume":"341","author":"Pitt B","year":"1999","unstructured":"B Pitt, F Zannad, W J Remme, R Cody, A Castaigne, A Perez, J Palensky, J Wittes N Engl J Med 341, 709\u2013717 (1999).","journal-title":"N Engl J Med"},{"key":"e_1_3_4_4_2","doi-asserted-by":"crossref","first-page":"342","DOI":"10.1001\/archinte.161.3.342","volume":"161","author":"Gomberg-Maitland M","year":"2001","unstructured":"M Gomberg-Maitland, D A Baran, V Fuster Arch Intern Med (Moscow) 161, 342\u2013352 (2001).","journal-title":"Arch Intern Med (Moscow)"},{"key":"e_1_3_4_5_2","doi-asserted-by":"crossref","first-page":"175","DOI":"10.1161\/01.CIR.92.2.175","volume":"92","author":"Lombes M","year":"1995","unstructured":"M Lombes, N Alfaidy, E Eugene, A Lessana, N Farman, J P Bonvalet Circulation 92, 175\u2013182 (1995).","journal-title":"Circulation"},{"key":"e_1_3_4_6_2","first-page":"S49","volume":"53","author":"Bonvalet J P","year":"1998","unstructured":"J P Bonvalet Kidney Int 53, Suppl. 65, S49\u2013S56 (1998).","journal-title":"Kidney Int"},{"key":"e_1_3_4_7_2","doi-asserted-by":"crossref","first-page":"835","DOI":"10.1016\/0092-8674(95)90199-X","volume":"83","author":"Mangelsdorf D J","year":"1995","unstructured":"D J Mangelsdorf, C Thummel, M Beato, P Herrlich, G Schutz, K Umesono, B Blumberg, P Kastner, M Mark, P Chambon, et al. Cell 83, 835\u2013839 (1995).","journal-title":"Cell"},{"key":"e_1_3_4_8_2","doi-asserted-by":"crossref","first-page":"119","DOI":"10.1126\/science.289.5476.119","volume":"289","author":"Geller D S","year":"2000","unstructured":"D S Geller, A Farhi, N Pinkerton, M Fradley, M Moritz, A Spitzer, G Meinke, F T Tsai, P B Sigler, R P Lifton Science 289, 119\u2013123 (2000).","journal-title":"Science"},{"key":"e_1_3_4_9_2","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1038\/966","volume":"19","author":"Geller D S","year":"1998","unstructured":"D S Geller, J Rodriguez-Soriano, A Vallo Boado, S Schifter, M Bayer, S S Chang, R P Lifton Nat Genet 19, 279\u2013281 (1998).","journal-title":"Nat Genet"},{"key":"e_1_3_4_10_2","doi-asserted-by":"crossref","first-page":"9424","DOI":"10.1073\/pnas.95.16.9424","volume":"95","author":"Berger S","year":"1998","unstructured":"S Berger, M Bleich, W Schmid, T J Cole, J Peters, H Watanabe, W Kriz, R Warth, R Greger, G Sch\u00fctz Proc Natl Acad Sci USA 95, 9424\u20139429 (1998).","journal-title":"Proc Natl Acad Sci USA"},{"key":"e_1_3_4_11_2","doi-asserted-by":"crossref","first-page":"3605","DOI":"10.1093\/nar\/23.17.3605","volume":"23","author":"Baron U","year":"1995","unstructured":"U Baron, S Freundlieb, M Gossen, H Bujard Nucleic Acids Res 23, 3605\u20133606 (1995).","journal-title":"Nucleic Acids Res"},{"key":"e_1_3_4_12_2","doi-asserted-by":"crossref","first-page":"691","DOI":"10.1161\/01.RES.79.4.691","volume":"79","author":"Yu Z","year":"1996","unstructured":"Z Yu, C S Redfern, G I Fishman Circ Res 79, 691\u2013697 (1996).","journal-title":"Circ Res"},{"key":"e_1_3_4_13_2","doi-asserted-by":"crossref","first-page":"C1343","DOI":"10.1152\/ajpcell.1996.270.5.C1343","volume":"270","author":"Escoubet B","year":"1996","unstructured":"B Escoubet, C Coureau, M Blot-Chabaud, J P Bonvalet, N Farman Am J Physiol 270, C1343\u2013C1353 (1996).","journal-title":"Am J Physiol"},{"key":"e_1_3_4_14_2","doi-asserted-by":"crossref","first-page":"493","DOI":"10.1083\/jcb.119.3.493","volume":"119","author":"Gavrieli Y","year":"1992","unstructured":"Y Gavrieli, Y Sherman, S A Ben-Sasson J Cell Biol 119, 493\u2013501 (1992).","journal-title":"J Cell Biol"},{"key":"e_1_3_4_15_2","doi-asserted-by":"crossref","first-page":"971","DOI":"10.1161\/01.HYP.26.6.971","volume":"26","author":"Robert V","year":"1995","unstructured":"V Robert, J S Silvestre, D Charlemagne, A Sabri, P Trouve, M Wassef, B Swynghedauw, C Delcayre Hypertension 26, 971\u2013978 (1995).","journal-title":"Hypertension"},{"key":"e_1_3_4_16_2","doi-asserted-by":"crossref","first-page":"602","DOI":"10.1016\/S0894-7317(05)80373-6","volume":"8","author":"Pollick C","year":"1995","unstructured":"C Pollick, S L Hale, R A Kloner J Am Soc Echocardiogr 8, 602\u2013610 (1995).","journal-title":"J Am Soc Echocardiogr"},{"key":"e_1_3_4_17_2","doi-asserted-by":"crossref","first-page":"1072","DOI":"10.1161\/01.CIR.58.6.1072","volume":"58","author":"Sahn D J","year":"1978","unstructured":"D J Sahn, A DeMaria, J Kisslo, A Weyman Circulation 58, 1072\u20131083 (1978).","journal-title":"Circulation"},{"key":"e_1_3_4_18_2","doi-asserted-by":"crossref","first-page":"401","DOI":"10.1016\/S0076-6879(00)27292-3","volume":"327","author":"Baron U","year":"2000","unstructured":"U Baron, H Bujard Methods Enzymol 327, 401\u2013421 (2000).","journal-title":"Methods Enzymol"},{"key":"e_1_3_4_19_2","doi-asserted-by":"crossref","first-page":"304","DOI":"10.1006\/meth.1999.0788","volume":"18","author":"Erickson R P","year":"1999","unstructured":"R P Erickson Methods 18, 304\u2013310 (1999).","journal-title":"Methods"},{"key":"e_1_3_4_20_2","doi-asserted-by":"crossref","first-page":"837","DOI":"10.1161\/01.RES.82.8.837","volume":"82","author":"Fishman G I","year":"1998","unstructured":"G I Fishman Circ Res 82, 837\u2013844 (1998).","journal-title":"Circ Res"},{"key":"e_1_3_4_21_2","first-page":"F181","volume":"280","author":"Farman N","year":"2001","unstructured":"N Farman, M E Rafestin-Oblin Am J Physiol 280, F181\u2013F192 (2001).","journal-title":"Am J Physiol"},{"key":"e_1_3_4_22_2","first-page":"893","volume":"120","author":"Brilla C G","year":"1992","unstructured":"C G Brilla, K T Weber J Lab Clin Med 120, 893\u2013901 (1992).","journal-title":"J Lab Clin Med"},{"key":"e_1_3_4_23_2","doi-asserted-by":"crossref","first-page":"2578","DOI":"10.1172\/JCI117269","volume":"93","author":"Young M","year":"1994","unstructured":"M Young, M Fullerton, R Dilley, J Funder J Clin Invest 93, 2578\u20132583 (1994).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_24_2","doi-asserted-by":"crossref","first-page":"967","DOI":"10.1097\/00004872-200105000-00018","volume":"19","author":"Gross V","year":"2001","unstructured":"V Gross, T Walther, A F Milia, K Walter, W Schneider, F C Luft J Hypertens 19, 967\u2013976 (2001).","journal-title":"J Hypertens"},{"key":"e_1_3_4_25_2","doi-asserted-by":"crossref","first-page":"974","DOI":"10.1161\/01.HYP.37.3.974","volume":"37","author":"Peng H","year":"2001","unstructured":"H Peng, O A Carretero, M E Alfie, J A Masura, N E Rhaleb Hypertension 37, 974\u2013980 (2001).","journal-title":"Hypertension"},{"key":"e_1_3_4_26_2","doi-asserted-by":"crossref","first-page":"1341","DOI":"10.1161\/01.RES.71.6.1341","volume":"71","author":"Mamuya W","year":"1992","unstructured":"W Mamuya, A Chobanian, P Brecher Circ Res 71, 1341\u20131350 (1992).","journal-title":"Circ Res"},{"key":"e_1_3_4_27_2","doi-asserted-by":"crossref","first-page":"2469","DOI":"10.1172\/JCI118305","volume":"96","author":"Hou J","year":"1995","unstructured":"J Hou, H Kato, R A Cohen, A V Chobanian, P Brecher J Clin Invest 96, 2469\u20132477 (1995).","journal-title":"J Clin Invest"},{"key":"e_1_3_4_28_2","doi-asserted-by":"crossref","first-page":"224","DOI":"10.1016\/S1043-2760(00)00270-8","volume":"11","author":"Young M","year":"2000","unstructured":"M Young, J W Funder Trends Endocrinol Metab 11, 224\u2013226 (2000).","journal-title":"Trends Endocrinol Metab"},{"key":"e_1_3_4_29_2","doi-asserted-by":"crossref","first-page":"38911","DOI":"10.1074\/jbc.M103984200","volume":"276","author":"Le Menuet D","year":"2001","unstructured":"D Le Menuet, R Isnard, M Bichara, S Viengchareun, M Muffat-Joly, F Walker, M C Zennaro, M Lombes J Biol Chem 276, 38911\u201338920 (2001).","journal-title":"J Biol Chem"},{"key":"e_1_3_4_30_2","doi-asserted-by":"crossref","first-page":"1207","DOI":"10.1016\/S0002-9149(00)00729-3","volume":"85","author":"Ramires F J","year":"2000","unstructured":"F J Ramires, A Mansur, O Coelho, M Maranhao, C J Gruppi, C Mady, J A Ramires Am J Cardiol 85, 1207\u20131211 (2000).","journal-title":"Am J Cardiol"},{"key":"e_1_3_4_31_2","doi-asserted-by":"crossref","first-page":"4826","DOI":"10.1073\/pnas.97.9.4826","volume":"97","author":"Redfern C H","year":"2000","unstructured":"C H Redfern, M Y Degtyarev, A T Kwa, N Salomonis, N Cotte, T Nanevicz, N Fidelman, K Desai, K Vranizan, E K Lee, et al. Proc Natl Acad Sci USA 97, 4826\u20134831 (2000).","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Proceedings of the National Academy of Sciences"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/pnas.org\/doi\/pdf\/10.1073\/pnas.102673599","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2022,6,7]],"date-time":"2022-06-07T01:40:43Z","timestamp":1654566043000},"score":1,"resource":{"primary":{"URL":"https:\/\/pnas.org\/doi\/full\/10.1073\/pnas.102673599"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2002,5,7]]},"references-count":31,"journal-issue":{"issue":"10","published-print":{"date-parts":[[2002,5,14]]}},"alternative-id":["10.1073\/pnas.102673599"],"URL":"https:\/\/doi.org\/10.1073\/pnas.102673599","relation":{},"ISSN":["0027-8424","1091-6490"],"issn-type":[{"value":"0027-8424","type":"print"},{"value":"1091-6490","type":"electronic"}],"subject":[],"published":{"date-parts":[[2002,5,7]]},"assertion":[{"value":"2001-12-17","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2002-05-07","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}