Chymase 1 (CMA1) (CMA1)

Chymase 1 (CMA1) is a chymotrypsin-like serine protease primarily synthesized and stored in the secretory granules of mast cells. In primates, including macaques and humans, it is the principal enzyme responsible for the angiotensin-converting enzyme (ACE)-independent conversion of angiotensin I to angiotensin II, especially in the heart and blood vessels (UniProt P49861). Chymase also plays a critical role in tissue remodeling and inflammation by activating various cytokines and enzymes, such as transforming growth factor-beta (TGF-beta) and matrix metalloproteinases (PubMed: 15507121). Because of its contribution to pathological fibrosis and cardiovascular remodeling, chymase is a target for drugs aimed at treating heart failure and chronic inflammatory diseases (PubMed: 30103338). Macaque chymase is frequently studied in preclinical research because it shares high sequence identity and functional similarity with human alpha-chymase, unlike rodent models which possess multiple chymase isoforms with differing substrate specificities (PubMed: 8626456). Therapeutic strategies focus on small molecule inhibitors that bind the active site to block enzymatic activity and mitigate the adverse effects of mast cell degranulation in tissues like the heart and lungs.

Other names

Mast cell protease 1Alpha-chymaseMast cell chymaseMacaque chymase

Inhibition of chymase enzymatic activity to prevent the conversion of Angiotensin I to Angiotensin II and the activation of pro-fibrotic factors like TGF-beta.