New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System: Chymase as an Important Target to Prevent Organ Damage
Chymase plays a crucial role in angiotensin II formation in various tissues. Angiotensin II induces gene expression of transforming growth factor (TGF)-β and matrix metalloproteinase (MMP)-9 precursors, and chymase can convert precursors of TGF-β and MMP-9 to their active forms. In cultured fibrobla...
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doaj-9ac2c1566e47442b9c7fcc1f82f3bf752020-11-24T23:59:50ZengElsevierJournal of Pharmacological Sciences1347-86132010-01-011134301309New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System: Chymase as an Important Target to Prevent Organ DamageShinji Takai0Denan Jin1Mizuo Miyazaki2Department of Pharmacology, Osaka Medical College, Daigaku-machi 2-7, Takatsuki City, Osaka 569-8686, Japan; Corresponding author. pha010@art.osaka-med.ac.jpDepartment of Pharmacology, Osaka Medical College, Daigaku-machi 2-7, Takatsuki City, Osaka 569-8686, JapanDepartment of Pharmacology, Osaka Medical College, Daigaku-machi 2-7, Takatsuki City, Osaka 569-8686, JapanChymase plays a crucial role in angiotensin II formation in various tissues. Angiotensin II induces gene expression of transforming growth factor (TGF)-β and matrix metalloproteinase (MMP)-9 precursors, and chymase can convert precursors of TGF-β and MMP-9 to their active forms. In cultured fibroblasts, significant increases in cell growth and TGF-β levels were observed after chymase injection; these increases were inhibited by a chymase inhibitor, but not by an angiotensin II–receptor blocker. In apolipoprotein E–deficient mice, abdominal aortic aneurysm (AAA) development depends on an increase in MMP-9 activities induced by angiotensin II infusion, but the inhibition of MMP-9 activation by a chymase inhibitor resulted in attenuation of the angiotensin II–induced AAA development. The upregulation of MMP-9 and TGF-β levels is involved in damage to various organs, but these gene expressions are not completely induced by angiotensin II alone. Therefore, chymase inhibition may be useful for attenuating MMP-9 and TGF-β levels, in addition to reducing angiotensin II formation, and this function may provide powerful organ protection. In this review, we propose the possible use of chymase inhibitors as agents to prevent organ damage. Keywords:: angiotensin II, angiotensin-converting enzyme, chymase, matrix metalloproteinase-9, transforming-growth factor-βhttp://www.sciencedirect.com/science/article/pii/S1347861319308965 |
collection |
DOAJ |
language |
English |
format |
Article |
sources |
DOAJ |
author |
Shinji Takai Denan Jin Mizuo Miyazaki |
spellingShingle |
Shinji Takai Denan Jin Mizuo Miyazaki New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System: Chymase as an Important Target to Prevent Organ Damage Journal of Pharmacological Sciences |
author_facet |
Shinji Takai Denan Jin Mizuo Miyazaki |
author_sort |
Shinji Takai |
title |
New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System: Chymase as an Important Target to Prevent Organ Damage |
title_short |
New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System: Chymase as an Important Target to Prevent Organ Damage |
title_full |
New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System: Chymase as an Important Target to Prevent Organ Damage |
title_fullStr |
New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System: Chymase as an Important Target to Prevent Organ Damage |
title_full_unstemmed |
New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System: Chymase as an Important Target to Prevent Organ Damage |
title_sort |
new approaches to blockade of the renin–angiotensin–aldosterone system: chymase as an important target to prevent organ damage |
publisher |
Elsevier |
series |
Journal of Pharmacological Sciences |
issn |
1347-8613 |
publishDate |
2010-01-01 |
description |
Chymase plays a crucial role in angiotensin II formation in various tissues. Angiotensin II induces gene expression of transforming growth factor (TGF)-β and matrix metalloproteinase (MMP)-9 precursors, and chymase can convert precursors of TGF-β and MMP-9 to their active forms. In cultured fibroblasts, significant increases in cell growth and TGF-β levels were observed after chymase injection; these increases were inhibited by a chymase inhibitor, but not by an angiotensin II–receptor blocker. In apolipoprotein E–deficient mice, abdominal aortic aneurysm (AAA) development depends on an increase in MMP-9 activities induced by angiotensin II infusion, but the inhibition of MMP-9 activation by a chymase inhibitor resulted in attenuation of the angiotensin II–induced AAA development. The upregulation of MMP-9 and TGF-β levels is involved in damage to various organs, but these gene expressions are not completely induced by angiotensin II alone. Therefore, chymase inhibition may be useful for attenuating MMP-9 and TGF-β levels, in addition to reducing angiotensin II formation, and this function may provide powerful organ protection. In this review, we propose the possible use of chymase inhibitors as agents to prevent organ damage. Keywords:: angiotensin II, angiotensin-converting enzyme, chymase, matrix metalloproteinase-9, transforming-growth factor-β |
url |
http://www.sciencedirect.com/science/article/pii/S1347861319308965 |
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