Effect of chymase inhibitor on vascular proliferation.
In vascular tissues, angiotensin II is potentially cleaved from angiotensin I by chymase and angiotensin-converting enzyme (ACE). In the normal state, vascular ACE regulates local angiotensin II formation and plays a crucial role in the regulation of blood pressure, whereas chymase is stored in mast cells and has no enzymatic activity. Chymase is activated immediately upon its release into the extracellular matrix in vascular tissues after mast cells have been activated by stimuli such as vessel injury by grafting or a balloon catheter. In dog grafted veins, chymase activity is increased, and the vascular proliferation is suppressed by either a chymase inhibitor or an angiotensin II receptor blocker. After balloon injury in dog vessels, chymase activity is significantly increased in the injured artery, and a chymase inhibitor is effective in preventing the vascular proliferation, but an ACE inhibitor is ineffective. Chymase plays an important role in the development of vascular proliferation via the induction of local angiotensin II formation in injured vessels.
Takai
Shinji
S
Department of Pharmacology, Osaka Medical College, Takatsuki City, Osaka, Japan. pha010@art.osaka-med.ac.jp
Miyazaki
Mizuo
M
D000800:Angioplasty, Balloon / Q000009:adverse effects; D000803:Angiotensin I / Q000096:biosynthesis / Q000502:physiology; D000804:Angiotensin II / Q000096:biosynthesis / Q000502:physiology*; D000818:Animals; D001158:Arteries / Q000201:enzymology / Q000473:pathology* / Q000637:transplantation; D002455:Cell Division / Q000187:drug effects; D053818:Chymases; D004285:Dogs; D008407:Mast Cells / Q000187:drug effects / Q000201:enzymology; D009131:Muscle, Smooth, Vascular / Q000473:pathology; D032389:Myocytes, Smooth Muscle / Q000473:pathology; D012697:Serine Endopeptidases / Q000502:physiology*; D015842:Serine Proteinase Inhibitors / Q000494:pharmacology*; D014680:Veins / Q000201:enzymology / Q000637:transplantation
D015842:Serine Proteinase Inhibitors; D000804:Angiotensin II; D000803:Angiotensin I; D012697:Serine Endopeptidases; D053818:Chymases