| Autor: |
Eickels, Martin van, Vetter, Hans, Grohé, Christian |
| Zdroj: |
British Journal of Pharmacology; December 2000, Vol. 131 Issue: 8 p1592-1596, 5p |
| Abstrakt: |
1 The effects of angiotensin-converting enzyme (ACE) inhibition and angiotensin type 1 (AT1) receptor blockade on insulin-like growth factor-I (IGF-I) induced proliferation and immediate-early-gene expression of neonatal rat cardiac fibroblasts were investigated. Moreover the role of the IGF-I receptor (IGF-IR) in this process was evaluated. 2 IGF-I (10−9 – 10−7 M) stimulated neonatal rat cardiac fibroblast growth in a dose-dependent fashion (maximum: 3.5±0.1 fold, 10−7 M), as determined by 5-bromo-2′-deoxyuridine (BrdU) incorporation. ACE inhibition or AT1 receptor blockade attenuated the IGF-I (10−7 M) induced neonatal rat cardiac fibroblast growth in a concentration-dependent fashion (moexiprilat: 50±2%, enalaprilat: 31±2%, CV11974; 58±1%, all: 10−7 M). 3 IGF-I stimulated cellular growth was accompanied by an upregulation of the immediate early genes c-Fos (2.4±0.3 fold), Egr-1 (4.7±1.1 fold) and Sp1 (6.2±0.7 fold). IGF-I induced expression was completely inhibited by ACE inhibition or AT1 receptor blockade. 4 Stimulation with IGF-I or Ang II (10−7 M) increased IGF-IR expression 5.7±0.5 fold and 3.6±0.5 fold respectively. The IGF-I induced overexpression of the IGF-IR was reduced by ACE inhibition with moexiprilat (10−7 M) by 79±7% and by AT1 receptor blockade with CV11974 (10−7 M) by 79±5%. 5 These data demonstrate that the mitogenic action of IGF-I in neonatal rat cardiac fibroblasts is in part mediated by activation of the renin-angiotensin system (RAS) with subsequent upregulation of IGF-IR expression. This observation has important implications for the treatment of cardiac diseases with ACE inhibitors alone and their combination with IGF-I or growth hormone. British Journal of Pharmacology (2000) 131, 1592 – 1596 |
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