OBJECTIVE: To determine the effects of fasudil, a Rho-kinase inhibitor, on mineralocorticoid-induced myocardial remodeling, we investigated whether fasudil would suppress myocardial fibrosis and inflammation in deoxycorticosterone-acetate (DOCA)/salt hypertensive rats. METHODS: Sprague-Dawley rats treated with DOCA combined with 1% NaCl and 0.2% KCl in the drinking water after receiving left nephrectomy were given fasudil (10 mg/kg/day; n = 20) or vehicle (n = 20). Systolic blood pressure (SBP) was measured biweekly. Myocardial monocyte/macrophage infiltration and myocardial fibrosis were determined histologically. Expressions of mRNA of procollagen I (PI), procollagen III (PIII), monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, type-1 plasminogen activator inhibitor (PAI-1), transforming growth factor (TGF)-beta1, and c-fos were determined. RESULTS: SBP was significantly increased on day 14 after treatment with DOCA/salt. Extent of interstitial and perivascular fibrosis was significantly increased on day 28. Expressions of mRNA of PI, PIII, MCP-1, IL-6, PAI-1, TGF-beta1, and c-fos were significantly increased on day 14. Although SBP did not differ between the fasudil and vehicle groups, extent of monocyte/macrophage infiltration and fibrosis was attenuated in the fasudil group. Expressions of mRNA of these factors except TGF-beta1 were also attenuated. CONCLUSION: Fasudil attenuates myocardial fibrosis possibly via suppression of monocyte/macrophage infiltration of the heart in DOCA/salt hypertensive rats.
OBJECTIVE: To determine the effects of fasudil, a Rho-kinase inhibitor, on mineralocorticoid-induced myocardial remodeling, we investigated whether fasudil would suppress myocardial fibrosis and inflammation in deoxycorticosterone-acetate (DOCA)/salthypertensiverats. METHODS:Sprague-Dawley rats treated with DOCA combined with 1% NaCl and 0.2% KCl in the drinking water after receiving left nephrectomy were given fasudil (10 mg/kg/day; n = 20) or vehicle (n = 20). Systolic blood pressure (SBP) was measured biweekly. Myocardial monocyte/macrophage infiltration and myocardial fibrosis were determined histologically. Expressions of mRNA of procollagen I (PI), procollagen III (PIII), monocyte chemoattractant protein (MCP)-1, interleukin (IL)-6, type-1 plasminogen activator inhibitor (PAI-1), transforming growth factor (TGF)-beta1, and c-fos were determined. RESULTS: SBP was significantly increased on day 14 after treatment with DOCA/salt. Extent of interstitial and perivascular fibrosis was significantly increased on day 28. Expressions of mRNA of PI, PIII, MCP-1, IL-6, PAI-1, TGF-beta1, and c-fos were significantly increased on day 14. Although SBP did not differ between the fasudil and vehicle groups, extent of monocyte/macrophage infiltration and fibrosis was attenuated in the fasudil group. Expressions of mRNA of these factors except TGF-beta1 were also attenuated. CONCLUSION:Fasudil attenuates myocardial fibrosis possibly via suppression of monocyte/macrophage infiltration of the heart in DOCA/salthypertensiverats.
Authors: Matthias Löhn; Oliver Plettenburg; Aimo Kannt; Markus Kohlmann; Armin Hofmeister; Dieter Kadereit; Peter Monecke; Alexander Schiffer; Anke Schulte; Hartmut Ruetten; Yuri Ivashchenko Journal: World J Cardiol Date: 2015-01-26
Authors: Jing Lin; Xiangyang Zhu; Alejandro R Chade; Kyra L Jordan; Ronit Lavi; Elena Daghini; Matthew E Gibson; Angelo Guglielmotti; Amir Lerman; Lilach O Lerman Journal: Arterioscler Thromb Vasc Biol Date: 2009-07-23 Impact factor: 8.311