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Pharmacologia Vol. 3 (1), 2012
Research Article
Chymase is a Target Enzyme for Prevention of Organ Damage
ShinjiTakai , Denan Jin and Mizuo Miyazaki
Abstract: Background: Organ damage is closely related in the upreglation of various key factors. Especially, angiotensin II and Transforming Growth Factor (TGF)-β play a crucial role in the cardiovascular remodeling and tissue fibrosis. Matrix metalloprotease (MMP)-9 is also related to the development and progression of various tissue remodeling. Chymase converts angiotensin I to angiotensin II and this enzyme can also convert precursors of TGF-β and MMP-9 to their active forms and its enzymatic function may play a crucial role in the development and the progression of organ damage. Results: Angiotensin II regulates blood pressure and plays an important role in cardiovascular remodeling. Chymase activities are augmented in the lesion of cardiovascular remodeling and its inhibition has shown the prevention of its remodeling via the reduction of angiotensin II. Moreover, chymase-activated MMP-9 also plays a crucial role in the cardiovascular remodeling and chymase inhibitors have shown the prevention of the remodeling via the suppression of MMP-9 activity. TGF-β is converted from its precursor by chymase and its inhibition results in the prevention of tissue fibrosis.Conclusion: Chymase is an important processing enzyme for angiotensin II, TGF-β and MMP-9, all of which are key factors for organ damage. Thus, chymase may be a key enzyme for organ damage and its inhibition may be useful for preventing various organ damages. We propose that chymase inhibitor may become a useful agent for prevention of organ damage in clinical settings.
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