The Role of Chymase in Vascular Remodeling and Tissue Fibrosis

Shinji      Takai; Denan      Jin; Michiko      Muramatsu; Mizuo      Miyazaki

Abstract

Chymase generates angiotensin II which plays a crucial role in vascular remodeling. In clinical studies, an angiotensin II receptor blocker was successful in preventing restenosis after percutaneous coronary intervention, but an angiotensin II-converting enzyme inhibitor was not. In dog, chymase activity was significantly increased in vessels injured by a balloon catheter, and a chymase inhibitor and an angiotensin II receptor blocker were effective in preventing the vascular proliferation, but an angiotensin-converting enzyme inhibitor was ineffective. Chymase also activates matrix metalloproteinase-9, and their function may play an important role in development of atherosclerosis and aneurysmal aorta. In human atherosclerosis and aneurysmal aorta, chymase activity was significantly increased. In the experimental models, chymase activity and mRNA level were also significantly increased in atherosclerotic lesions and aneurysmal aorta, but chymase inhibitors prevented the vascular remodeling. On the other hand, chymase activates latent transforming growth factor-β-binding protein to transforming growth factor-β, and its function may be related in promoting tissue fibrosis. Chymase promotes activations of angiotensin II, matrix metalloproteinase-9 and transforming growth factor-β, and chymase inhibitors may promise to prevent vascular remodeling and tissue fibrosis.

Keywords: chymase, angiotensin II, mast cells, matrix metalloproteinase, transforming growth factor

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