Chymase inhibition as a pharmacological target: a role in inflammatory and functional gastrointestinal disorders?

S Heuston, NP Hyland

Chymase has been extensively studied with respect to its role in the pathophysiology of cardiovascular disease, and is notable for its role in the generation of angiotensin II, a mediator crucial in vascular remodelling. However, in more recent years, an association between chymase and several inflammatory diseases, including gastrointestinal (GI) disorders such as inflammatory bowel diseases (IBD) have been described. Such studies, to date, with respect to IBD at least, are descriptive in the clinical context; nonetheless, preclinical studies implicate chymase in the pathogenesis of gut inflammation. However, studies to elucidate the role of chymase in functional bowel disease are in their infancy, but suggest a plausible role for chymase in contributing to some of the phenotypic changes observed in such disorders, namely increased epithelial permeability. In this short review, we have summarized the current knowledge on the pathophysiological role of chymase and its inhibition with reference to inflammation and tissue injury outside of the GI tract and discussed its potential role in GI disorders. We speculate that chymase may be a novel therapeutic target in the GI tract, and as such, inhibitors of chymase warrant preclinical investigation in GI diseases.