Improvement of cardiovascular remodelling by chymase inhibitor.

Abstract

Chymase has been identified as an angiotensin II-forming enzyme found in cardiovascular tissues. Angiotensin II is involved not only in the regulation of blood pressure, but also in the progression of cardiovascular remodelling. Interestingly, chymase inhibitors prevent cardiovascular remodelling without lowering blood pressure. The reason why chymase inhibitors do not affect blood pressure may depend on the localization of chymase invivo. In normal tissues, chymase is stored in mast cell granules and has no enzymatic function; whereas, in damaged tissues, chymase exhibits enzymatic activity immediately following its release from the granules. Chymase also activates transforming growth factor-β and matrix metalloproteinase-9, both of which are involved in cardiovascular remodelling, and their enzymatic functions are also observed only in damaged tissues. In animal models of hypertension, diabetes and hypercholesterolaemia, chymase inhibitors improve cardiovascular remodelling without a general circulatory effect, including blood pressure. Thus, it is proposed that chymase is a potentially important target for preventing cardiovascular diseases.