Abstract
INTRODUCTION: Non-angiotensin converting enzyme mechanisms of angiotensin II production remain underappreciated in part due to the success of current therapies to ameliorate the impact of primary hypertension and atherosclerotic diseases of the heart and the blood vessels. This review scrutinize the current literature to highlight chymase role as a critical participant in the pathogenesis of cardiovascular disease and heart failure. AREAS COVERED: We review the contemporaneous understanding of circulating and tissue biotransformation mechanisms of the angiotensins focusing on the role of chymase as an alternate tissue generating pathway for angiotensin II pathological mechanisms of action. EXPERT OPINION: While robust literature documents the singularity of chymase as an angiotensin II-forming enzyme, particularly when angiotensin converting enzyme is inhibited, this knowledge has not been fully recognized to clinical medicine. This review discusses the limitations of clinical trials' that explored the benefits of chymase inhibition in accounting for the failure to duplicate in humans what has been demonstrated in experimental animals.