Will chymase inhibitors be the next major development for the treatment of cardiovascular disorders?

• Published in: Expert opinion on investigational drugs Vol. 12; no. 8; p. 1429
• Main Authors: Doggrell, Sheila A, Wanstall, Janet C
• Format: Journal Article
• Language: English
• Published: England 01-08-2003
• Subjects: Acetamides - administration & dosage; Acetamides - therapeutic use; Animals; Azetidines - administration & dosage; Azetidines - therapeutic use; Benzoates - administration & dosage; Benzoates - therapeutic use; Cardiovascular Diseases - drug therapy; Cardiovascular Diseases - enzymology; Cardiovascular Diseases - pathology; Chymases; Disease Models, Animal; Humans; Pyrimidines - administration & dosage; Pyrimidines - therapeutic use; Serine Endopeptidases - metabolism; Serine Proteinase Inhibitors - administration & dosage; Serine Proteinase Inhibitors - therapeutic use; Tunica Intima - drug effects; Tunica Intima - enzymology; Tunica Intima - pathology
• ISSN: 1354-3784
• DOI: 10.1517/13543784.12.8.1429

Chymase is contained in the secretory granules of mast cells. In addition to the synthesis of angiotensin II, chymase is involved in transforming growth factor-beta activation and cleaves Type I procollagen to produce collagen. NK301 and BCEAB are orally-active inhibitors of chymase. NK301 was tested in a dog model of vascular intimal hyperplasia after balloon injury and shown to reduce the increased chymase activity in the injured arteries and prevent intimal thickening. In a hamster model of cardiac fibrosis associated with cardiomyopathy, BCEAB reduced the increased cardiac chymase activity in cardiomyopathy and reduced fibrosis. Chymase inhibitors may be an important development for the treatment of cardiovascular injury associated with mast cell degranulation.