New Approaches to Blockade of the Renin–Angiotensin–Aldosterone System:Chymase as an Important Target to Prevent Organ Damage

Journal of Pharmacological Sciences

Shinji Takai¹  Mizuo Miyazaki¹  Denan Jin¹ 

[1] Department of Pharmacology, Osaka Medical College, Japan

关键词: angiotensin II;    angiotensin-converting enzyme;    chymase;    matrix metalloproteinase-9;    transforming growth factor-β;   

DOI  :  10.1254/jphs.10R05FM

学科分类：药学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(75)Cited-By(20)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.

【 授权许可】

Unknown