{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T14:07:17Z","timestamp":1791295637347,"version":"4.1.0"},"reference-count":49,"publisher":"Ovid Technologies (Wolters Kluwer Health)","issue":"5","content-domain":{"domain":["www.ahajournals.org"],"crossmark-restriction":true},"short-container-title":["Hypertension"],"published-print":{"date-parts":[[2001,11]]},"abstract":"<jats:p>Cardiac extracellular matrix undergoes extensive and continuous turnover involved in the lesion-reparation process, such as in cardiac remodeling, in hypertensive cardiac hypertrophy, in dilated cardiomyopathy, after myocardial infarction in the transition to heart failure, and during the progression of left ventricular dysfunction. Cardiac fibrosis is a major determinant of diastolic dysfunction and pumping capacity, and it may provide the structural substrate for arrhythmogenicity, thus potentially contributing the to progression of heart failure and sudden death. Aldosterone was shown to promote cardiac fibrosis in various experimental models. It was demonstrated that spironolactone may oppose the effect of aldosterone in promoting cardiac fibrosis. Measurement of cardiac collagen turnover by use of serological markers is a useful tool for monitoring cardiac tissue repair and fibrosis in experimental models or clinical conditions. We found that high serum levels of a marker of collagen turnover (procollagen type III N-terminal peptide ) in patients with chronic heart failure receiving conventional therapy, including ACE inhibitors, was associated with high mortality and hospitalization rates. In RALES (Randomized Aldactone Evaluation Study), in patients randomized to placebo, markers continued to increase or remained unchanged after 6-month follow-up. On the contrary, adding spironolactone 25 mg daily significantly decreased the levels of these serum markers during the same period. Most importantly, the spironolactone-related morbidity and mortality benefit was most predominant in subgroups with highest baseline levels of serum markers. These results suggest that limitation of the aldosterone-related excessive extracellular matrix turnover may be one of the various extrarenal mechanisms contributing to the beneficial effect of spironolactone in patients with chronic heart failure.<\/jats:p>","DOI":"10.1161\/hy1101.099484","type":"journal-article","created":{"date-parts":[[2007,9,28]],"date-time":"2007-09-28T18:37:17Z","timestamp":1191004637000},"page":"1227-1232","update-policy":"https:\/\/doi.org\/10.1161\/crossmarkpolicy","source":"Crossref","is-referenced-by-count":105,"title":["Treatment of Congestive Heart Failure"],"prefix":"10.1161","volume":"38","author":[{"given":"Faiez","family":"Zannad","sequence":"first","affiliation":[{"name":"From the Centre d\u2019Investigation Clinique INSERM-CHU and Department Of Cardiology (F.Z., F.A.) and the Department of Biochemistry (B.D.), Centre Hospitalier Universitaire, Equipe d\u2019Accueil EA 2403, University Henri Poincare\u0301, Nancy, France,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Brigitte","family":"Dousset","sequence":"additional","affiliation":[{"name":"From the Centre d\u2019Investigation Clinique INSERM-CHU and Department Of Cardiology (F.Z., F.A.) and the Department of Biochemistry (B.D.), Centre Hospitalier Universitaire, Equipe d\u2019Accueil EA 2403, University Henri Poincare\u0301, Nancy, France,"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Franc\u0327ois","family":"Alla","sequence":"additional","affiliation":[{"name":"From the Centre d\u2019Investigation Clinique INSERM-CHU and Department Of Cardiology (F.Z., F.A.) and the Department of Biochemistry (B.D.), Centre Hospitalier Universitaire, Equipe d\u2019Accueil EA 2403, University Henri Poincare\u0301, Nancy, France,"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"276","reference":[{"key":"e_1_3_1_1_2","first-page":"330","volume":"68","year":"1995","unstructured":"Butt RP, Laurent GJ, Bishop JE. Collagen production and replication by cardiac fibroblasts is enhanced in response to diverse classes of growth factors. Eur J Cell Biol. 1995; 68: 330\u2013335.","journal-title":"Eur J Cell Biol"},{"key":"e_1_3_1_2_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00226785"},{"key":"e_1_3_1_3_2","doi-asserted-by":"publisher","DOI":"10.1007\/978-1-4615-5385-4_4"},{"key":"e_1_3_1_4_2","doi-asserted-by":"publisher","DOI":"10.1016\/0167-4889(95)00205-7"},{"key":"e_1_3_1_5_2","first-page":"101","volume":"26","year":"1997","unstructured":"Liu YH, Yang XP, Sharov VG, Nass O, Sabbah HN, Peterson E, Carretero OA. Effects of angiotensin converting enzyme inhibitors and angiotensin II type 1 receptor antagonists in rats with heart failure. J Clin Invest. 1997; 26: 101\u2013111.","journal-title":"J Clin Invest"},{"key":"e_1_3_1_6_2","doi-asserted-by":"publisher","DOI":"10.1152\/physrev.1999.79.1.215"},{"key":"e_1_3_1_7_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.99.21.2750"},{"key":"e_1_3_1_8_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1993.1021"},{"key":"e_1_3_1_9_2","doi-asserted-by":"publisher","DOI":"10.1172\/JCI115414"},{"key":"e_1_3_1_10_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.37.3.827"},{"key":"e_1_3_1_11_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.12.1388"},{"key":"e_1_3_1_12_2","doi-asserted-by":"publisher","DOI":"10.1093\/ajh\/7.1.52"},{"key":"e_1_3_1_13_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.35.6.1197"},{"key":"e_1_3_1_14_2","doi-asserted-by":"publisher","DOI":"10.1161\/hyp.37.3.833"},{"key":"e_1_3_1_15_2","doi-asserted-by":"publisher","DOI":"10.1006\/jmcc.1996.0023"},{"key":"e_1_3_1_16_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.5.491"},{"key":"e_1_3_1_17_2","first-page":"2488","volume":"96","year":"1997","unstructured":"Weber KT. Monitoring tissue repair and fibrosis from a distance. Circulation. 1997; 96: 2488\u20132492.","journal-title":"Circulation"},{"key":"e_1_3_1_18_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.96.8.2565"},{"key":"e_1_3_1_19_2","doi-asserted-by":"publisher","DOI":"10.1136\/hrt.78.5.505"},{"key":"e_1_3_1_20_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)80251-3"},{"key":"e_1_3_1_21_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0002-9149(99)80686-9"},{"key":"e_1_3_1_22_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.91.5.1450"},{"key":"e_1_3_1_23_2","first-page":"1729","volume":"201","year":"2000","unstructured":"Querejeta R, Varo N, Lopez B, Larman M, Artinano E, Etayo JC, Martinez Ubago JL, Gutierrez-Stampa M, Emparanza JI, Gil MJ, Monreal M, Mindan JP, Diez J. Serum carboxy-terminal propeptide of procollagen type I is a marker of myocardial fibrosis in hypertensive heart disease. Circulation. 2000; 201: 1729\u20131735.","journal-title":"Circulation"},{"key":"e_1_3_1_24_2","doi-asserted-by":"publisher","DOI":"10.1053\/euhj.2000.2370"},{"key":"e_1_3_1_25_2","doi-asserted-by":"publisher","DOI":"10.1253\/jcj.49.171"},{"key":"e_1_3_1_26_2","doi-asserted-by":"publisher","DOI":"10.1093\/clinchem\/36.7.1328"},{"key":"e_1_3_1_27_2","doi-asserted-by":"publisher","DOI":"10.1016\/0270-9139(95)94132-0"},{"key":"e_1_3_1_28_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.81.1.2297848"},{"key":"e_1_3_1_29_2","first-page":"1669","year":"1991","unstructured":"Peuhkurinen KJ, Risteli L, Melkko J, Linnaluoto M, Jounela A, Risteli J. Thrombolytic therapy with streptokinase stimulates collagen breakdown. Circulation. 1991; 1669\u20131975.","journal-title":"Circulation"},{"key":"e_1_3_1_30_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.101.13.1527"},{"key":"e_1_3_1_31_2","doi-asserted-by":"publisher","DOI":"10.1161\/circ.102.22.2700"},{"key":"e_1_3_1_32_2","doi-asserted-by":"publisher","DOI":"10.1002\/(SICI)1097-0258(20000115)19:1<113::AID-SIM245>3.0.CO;2-O"},{"key":"e_1_3_1_33_2","first-page":"734","volume":"34","year":"1999","unstructured":"Zannad F, Briancon S, Juilliere Y, Mertes PM, Villemot JP, Alla F, Virion JM. Incidence, clinical and etiologic features, and outcomes of advanced chronic heart failure: the EPICAL Study; Epid\u00e9miologie de l\u2019insuffisance cardiaque avanc\u00e9e en Lorraine. J Am Coll Cardiol. 1999; 34: 734\u2013742.","journal-title":"J Am Coll Cardiol"},{"key":"e_1_3_1_34_2","first-page":"2145","volume":"131","year":"1991","unstructured":"Woessner JF Jr. Matrix metalloproteinases and their inhibitors in connective tissue remodeling. FASEB J. 1991; 131: 2145\u20132154.","journal-title":"FASEB J"},{"key":"e_1_3_1_35_2","doi-asserted-by":"publisher","DOI":"10.1016\/0163-7258(93)90074-N"},{"key":"e_1_3_1_36_2","doi-asserted-by":"publisher","DOI":"10.1161\/01.CIR.103.1.72"},{"key":"e_1_3_1_37_2","doi-asserted-by":"publisher","DOI":"10.1358\/mf.1999.21.3.534832"},{"key":"e_1_3_1_38_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(99)00088-7"},{"key":"e_1_3_1_39_2","doi-asserted-by":"publisher","DOI":"10.1007\/BF00180074"},{"key":"e_1_3_1_40_2","doi-asserted-by":"crossref","first-page":"12A","DOI":"10.1016\/0002-9149(93)90239-9","volume":"71","year":"1993","unstructured":"Brilla CG, Matsubara LS, Weber KT. Antifibrotic effects of spironolactone in preventing myocardial fibrosis in systemic arterial hypertension. Am J Cardiol. 1993; 71: 12A\u201316A.","journal-title":"Am J Cardiol"},{"key":"e_1_3_1_41_2","doi-asserted-by":"publisher","DOI":"10.1093\/cvr\/26.7.671"},{"key":"e_1_3_1_42_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0735-1097(00)01129-3"},{"key":"e_1_3_1_43_2","doi-asserted-by":"publisher","DOI":"10.1016\/S0008-6363(97)00091-6"},{"key":"e_1_3_1_44_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411001"},{"key":"e_1_3_1_45_2","doi-asserted-by":"publisher","DOI":"10.1056\/NEJM199909023411009"},{"key":"e_1_3_1_46_2","doi-asserted-by":"publisher","DOI":"10.1016\/0002-9149(93)90132-V"},{"key":"e_1_3_1_47_2","doi-asserted-by":"publisher","DOI":"10.1093\/eurheartj\/16.suppl_N.98"},{"key":"e_1_3_1_48_2","doi-asserted-by":"publisher","DOI":"10.1067\/mhj.2001.111258"},{"key":"e_1_3_1_49_2","doi-asserted-by":"publisher","DOI":"10.1023\/A:1011119003788"}],"container-title":["Hypertension"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.ahajournals.org\/doi\/full\/10.1161\/hy1101.099484","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2024,5,14]],"date-time":"2024-05-14T02:19:06Z","timestamp":1715653146000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.ahajournals.org\/doi\/10.1161\/hy1101.099484"}},"subtitle":["Interfering the Aldosterone-Cardiac Extracellular Matrix Relationship"],"short-title":[],"issued":{"date-parts":[[2001,11]]},"references-count":49,"journal-issue":{"issue":"5","published-print":{"date-parts":[[2001,11]]}},"alternative-id":["10.1161\/hy1101.099484"],"URL":"https:\/\/doi.org\/10.1161\/hy1101.099484","relation":{},"ISSN":["0194-911X","1524-4563"],"issn-type":[{"value":"0194-911X","type":"print"},{"value":"1524-4563","type":"electronic"}],"subject":[],"published":{"date-parts":[[2001,11]]},"assertion":[{"value":"2001-08-08","order":0,"name":"received","label":"Received","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-09-10","order":1,"name":"accepted","label":"Accepted","group":{"name":"publication_history","label":"Publication History"}},{"value":"2001-11-01","order":2,"name":"published","label":"Published","group":{"name":"publication_history","label":"Publication History"}}]}}