[Role of chymase in vascular diseases and the efficacy of chymase inhibitor].
In vascular tissues, angiotensin II is cleaved from angiotensin I by chymase and angiotensin converting enzyme (ACE). In the normal state, chymase is stored in mast cells and has no angiotensin II-forming activity, while chymase is activated immediately where mast cells have been activated by local stimuli. A clinical trial of an angiotensin receptor blocker (ARB) for preventing restenosis after percutaneous transluminal coronary angioplasty was successful, but that of an ACE inhibitor was not. After balloon injury in dog vessels, chymase activity was significantly increased in the injured artery, and a chymase inhibitor and an ARB were effective in preventing the vascular proliferation, but an ACE inhibitor was ineffective. In dog grafted veins, intimal area, chymase activity, and angiotensin II concentration were significantly increased after the operation, while they were significantly suppressed by a chymase inhibitor. However, the chymase inhibitor, unlike ACE inhibitor and ARB, did not affect blood pressure. These reports indicate that local angiotensin II production by chymase is involved only in the injured vessels. Therefore, a chymase inhibitor may be useful for preventing vascular disorders without affecting blood pressure.
Takai
Shinji
S
Department of Pharmacology, Osaka Medical College, Japan. pha010@art.osaka-med.ac.jp
D015906:Angioplasty, Balloon, Coronary; D000804:Angiotensin II / Q000096:biosynthesis; D000818:Animals; D001794:Blood Pressure; D053818:Chymases; D023903:Coronary Restenosis / Q000517:prevention & control; D015195:Drug Design; D006083:Graft Occlusion, Vascular / Q000517:prevention & control; D006801:Humans; D008407:Mast Cells / Q000201:enzymology; D012697:Serine Endopeptidases / Q000502:physiology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology* / Q000627:therapeutic use; D014652:Vascular Diseases / Q000517:prevention & control*
D015842:Serine Proteinase Inhibitors; D000804:Angiotensin II; D012697:Serine Endopeptidases; D053818:Chymases