Abstract
The renin-angiotensin system (RAS) is frequently activated in the patients with chronic liver diseases, and recent studies have shown that RAS plays a pivotal role in the progression of chronic liver diseases, i.e., liver fibrosis and hepatocellular carcinoma (HCC). Angiotensin-II (AT-II) reportedly stimulates contractility and proliferation of the activated hepatic stellate cells, and increases the transforming growth factor-β (TGF-β) expression through angiotensin type-I receptors (AT1-R). Many studies have demonstrated that the clinically used angiotensin-converting enzyme inhibitors (ACE-I) and AT1-R blockers (ARB) significantly attenuated the liver fibrosis development in the experimental studies and clinical practice. AT-II also strongly promotes neovascularization, which plays a pivotal role in tumor development. AT-II induces a potent angiogenic factor; namely, the vascular endothelial growth factor (VEGF). It has been reported that ACE-I significantly attenuated the experimental HCC growth and hepatocarcinogenesis along with suppression of neovascularization. The VEGF expression in the tumor was suppressed by ACE-I, too. The combined treatment of ACE-I with other clinically used agents, such as interferon, imatinib mesylate, and vitamin K, shows more potent inhibitory effects on the development of liver fibrosis and HCC. Since RAS inhibitors are widely used in the clinical practice without serious side effects, they may represent a potential new therapeutic strategy against the progression of chronic liver diseases.
Keywords: Renin-angiotensin system, angiotensin-II, angiogenesis, liver fibrosis, hepatocellular carcinoma, vascular endothelial growth factor
Current Medicinal Chemistry
Title: Renin-Angiotensin System Inhibitors as Therapeutic Alternatives in the Treatment of Chronic Liver Diseases
Volume: 14 Issue: 26
Author(s): Hitoshi Yoshiji, Ryuichi Noguchi, Yasuhide Ikenaka, Mitsuteru Kitade, Kosuke Kaji, Tatsuhiro Tsujimoto, Masahito Uemura and Hiroshi Fukui
Affiliation:
Keywords: Renin-angiotensin system, angiotensin-II, angiogenesis, liver fibrosis, hepatocellular carcinoma, vascular endothelial growth factor
Abstract: The renin-angiotensin system (RAS) is frequently activated in the patients with chronic liver diseases, and recent studies have shown that RAS plays a pivotal role in the progression of chronic liver diseases, i.e., liver fibrosis and hepatocellular carcinoma (HCC). Angiotensin-II (AT-II) reportedly stimulates contractility and proliferation of the activated hepatic stellate cells, and increases the transforming growth factor-β (TGF-β) expression through angiotensin type-I receptors (AT1-R). Many studies have demonstrated that the clinically used angiotensin-converting enzyme inhibitors (ACE-I) and AT1-R blockers (ARB) significantly attenuated the liver fibrosis development in the experimental studies and clinical practice. AT-II also strongly promotes neovascularization, which plays a pivotal role in tumor development. AT-II induces a potent angiogenic factor; namely, the vascular endothelial growth factor (VEGF). It has been reported that ACE-I significantly attenuated the experimental HCC growth and hepatocarcinogenesis along with suppression of neovascularization. The VEGF expression in the tumor was suppressed by ACE-I, too. The combined treatment of ACE-I with other clinically used agents, such as interferon, imatinib mesylate, and vitamin K, shows more potent inhibitory effects on the development of liver fibrosis and HCC. Since RAS inhibitors are widely used in the clinical practice without serious side effects, they may represent a potential new therapeutic strategy against the progression of chronic liver diseases.
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Yoshiji Hitoshi, Noguchi Ryuichi, Ikenaka Yasuhide, Kitade Mitsuteru, Kaji Kosuke, Tsujimoto Tatsuhiro, Uemura Masahito and Fukui Hiroshi, Renin-Angiotensin System Inhibitors as Therapeutic Alternatives in the Treatment of Chronic Liver Diseases, Current Medicinal Chemistry 2007; 14 (26) . https://dx.doi.org/10.2174/092986707782360169
DOI https://dx.doi.org/10.2174/092986707782360169 |
Print ISSN 0929-8673 |
Publisher Name Bentham Science Publisher |
Online ISSN 1875-533X |
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