{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T02:07:39Z","timestamp":1791252459765,"version":"4.1.0"},"reference-count":53,"publisher":"Wiley","issue":"9","license":[{"start":{"date-parts":[[2006,5,23]],"date-time":"2006-05-23T00:00:00Z","timestamp":1148342400000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/onlinelibrary.wiley.com\/termsAndConditions#vor"}],"funder":[{"DOI":"10.13039\/501100000274","name":"British Heart Foundation","doi-asserted-by":"publisher","id":[{"id":"10.13039\/501100000274","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":["faseb.onlinelibrary.wiley.com"],"crossmark-restriction":true},"short-container-title":["The FASEB Journal"],"published-print":{"date-parts":[[2006,7]]},"abstract":"<jats:title>ABSTRACT<\/jats:title>\n                  <jats:p>\n                    Angiotensin (ANG) II (AngII) and aldosterone contribute to the development of interstitial cardiac fibrosis. We investigated the potential role of a Nox2\u2010containing NADPH oxidase in aldosterone\u2010induced fibrosis and the involvement of this mechanism in AngII\u2010induced effects. Nox2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    mice were compared with matched wild\u2010type controls (WT). In WT mice, subcutaneous (s.c.) AngII (1.1 mg\/kg\/day for 2 wk) significantly increased NADPH oxidase activity, interstitial fibrosis (11.5\u00b11.0% vs. 7.2\u00b10.7%;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05), expression of fibronectin, procollagen I, and connective tissue growth factor mRNA, MMP\u20102 activity, and NF\u2010kB activation. These effects were all inhibited in Nox2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    hearts. The mineralocorticoid receptor antagonist spironolactone inhibited AngII\u2010induced increases in NADPH oxidase activity and the increase in interstitial fibrosis. In a model of mineralocorticoid\u2010dependent hypertension involving chronic aldosterone infusion (0.2 mg\/kg\/day) and a 1% Na Cl diet (\u201cALDO\u201d), WT animals exhibited increased NADPH oxidase activity, pro\u2010fibrotic gene expression, MMP\u20102 activity, NF\u2010kB activation, and significant interstitial cardiac fibrosis (12.0\u00b11.7% with ALDO vs. 6.3\u00b10.3% without;\n                    <jats:italic>P<\/jats:italic>\n                    &lt;0.05). These effects were inhibited in Nox2\n                    <jats:sup>\u2212\/\u2212<\/jats:sup>\n                    ALDO mice (e.g., fibrosis 6.8\u00b10.8% with ALDO vs. 5.8\u00b11.0% without ALDO;\n                    <jats:italic>P<\/jats:italic>\n                    =NS). These results suggest that aldosterone\u2010dependent activation of a Nox2\u2010containing NADPH oxidase contributes to the profibrotic effect of AngII in the heart as well as the fibrosis seen in mineralocorticoid\u2010dependent hypertension.\u2014Johar, S., Cave, A. C., Narayanapanicker, A., Grieve, D. J., Shah, A. M. Aldosterone mediates angiotensin II\u2010induced interstitial cardiac fibrosis via a Nox2\u2010containing NADPH oxidase.\n                    <jats:italic>FASEB J.<\/jats:italic>\n                    20, E846\u2013E854 (2006)\n                  <\/jats:p>","DOI":"10.1096\/fj.05-4642fje","type":"journal-article","created":{"date-parts":[[2006,5,24]],"date-time":"2006-05-24T00:04:14Z","timestamp":1148429054000},"page":"1546-1548","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":279,"title":["Aldosterone mediates angiotensin II\u2010induced interstitial cardiac fibrosis via a Nox2\u2010containing NADPH oxidase"],"prefix":"10.1096","volume":"20","author":[{"given":"Sofian","family":"Johar","sequence":"first","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison C.","family":"Cave","sequence":"additional","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anilkumar","family":"Narayanapanicker","sequence":"additional","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Grieve","sequence":"additional","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay M.","family":"Shah","sequence":"additional","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Sofian","family":"Johar","sequence":"additional","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alison C.","family":"Cave","sequence":"additional","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Anilkumar","family":"Narayanapanicker","sequence":"additional","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"David J.","family":"Grieve","sequence":"additional","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ajay M.","family":"Shah","sequence":"additional","affiliation":[{"name":"King's College London Cardiovascular Division  London UK"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"311","published-online":{"date-parts":[[2006,5,23]]},"reference":[{"key":"e_1_2_6_2_1","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.215"},{"key":"e_1_2_6_3_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.96.11.4065"},{"key":"e_1_2_6_4_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.RES.67.6.1355"},{"key":"e_1_2_6_5_1","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.98.24.2765"},{"key":"e_1_2_6_6_1","first-page":"475","article-title":"Myocardial fibrosis associated with aldosterone or angiotensin II administration: attenuation by calcium channel blockade","volume":"30","author":"Ramires F. 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