Chymase

Chymase is a serine protease belonging to the chymotrypsin family, predominantly expressed in mast cells. It is stored in secretory granules and released upon mast cell degranulation in response to allergic or inflammatory stimuli. In humans, tissue-localized chymase contributes to the formation of angiotensin II from angiotensin I within the heart and blood vessel walls, providing a pathway for local Ang II production independent of circulating ACE.

Beyond angiotensin processing, chymase exhibits broad proteolytic activity on extracellular matrix components and other precursor proteins, influencing tissue remodeling and fibrosis in chronic inflammatory conditions. Its actions have been implicated in cardiovascular disease, atherogenesis, and allergic inflammation, where mast cell–derived proteases contribute to pathology in a tissue-dependent manner.

Species differences are substantial: rodent chymases differ in substrate specificity and distribution, complicating extrapolation to humans and affecting the interpretation of animal studies.

Therapeutic targeting of chymase has been explored in preclinical models and early-stage trials, with chymase inhibitors investigated for reducing fibrosis and adverse remodeling after myocardial infarction and in chronic kidney or liver diseases. No chymase-targeted drug has yet gained broad clinical approval.