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Lookup NU author(s): Professor Albert Geerts
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1 Previous in vivo studies in men and experimental animal models have shown that hyperaldosteronemia is correlated with cardiac fibrosis due to increased total collagen synthesis. As yet, it is unclear whether aldosterone has direct pro-fibrogenic effect on cardiac fibroblasts, the fibrogenic effector cell in the myocardium, and if so which procollagens specifically are synthesized at higher rates. 2 The present study aims at establishing whether tie novo collagen synthesis by cardiac fibroblasts is enhanced following exposure for 2 x 24 h to pharmacological (10(-7)-10(-8) M), near-physiological (10(-9) M) or physiological (10(-10)-10(-11) M) aldosterone concentrations. During the last 24 h, cells were metabolically labelled with [S-35]-methioninel/[S-35]-cysteine. Labelled procollagens were immunoprecipitated quantitatively using antibodies against specific procollagens. Contrary to expectations, 10(-7) M aldosterone inhibited significantly tie novo synthesis of procollagens type I and IV (-35% and -42%, respectively). For procollagen type III, only a tendency towards inhibition was observed. At lower concentrations of aldosterone (10(-8)-10(-10) M), synthesis of procollagens type I, III or IV was unaffected. 3 Cellular DNA synthesis under influence of aldosterone was evaluated by measuring BrdU incorporation. Cells were treated with aldosterone, while BrdU was added during the last 16 h of treatment. Aldosterone had no demonstrable effect on cellular proliferation. 4 Reverse transcription-polymerase chain reaction (RT-PCR) clearly demonstrated the presence of mineralocorticoid receptor mRNA in cardiac fibroblasts. 5 In spite of the expression of the mineralocorticoid receptor by cultured cardiac fibroblasts. the pro-fibrogenic effect of aldosterone as observed in vivo, is not likely to be due to a direct effect of this hormone in cardiac fibroblasts.
Author(s): Rombouts K, Wielant A, Hellemans K, Schuppan D, Geerts A
Publication type: Article
Publication status: Published
Journal: British Journal of Pharmacology
Year: 2001
Volume: 134
Issue: 1
Pages: 224-232
ISSN (print): 0007-1188
ISSN (electronic): 1476-5381
Publisher: John Wiley & Sons Ltd.
URL: http://dx.doi.org/10.1038/sj.bjp.0704247
DOI: 10.1038/sj.bjp.0704247
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