Angiotensin-converting enzyme-independent pathways of angiotensin II formation in human tissues and cardiovascular diseases.

The tissue renin-angiotensin system plays an integral role in the homeostasis of blood pressure and in the pathogenesis of cardiovascular remodeling. These effects are primarily mediated through the paracrine and autocrine actions of locally produced angiotensin II (A II). It is generally accepted that the conversion of angiotension I to A II is mainly due to angiotensin-converting enzyme (ACE). However, there are several in vitro and in vivo reports of ACE-independent synthesis of A II in hypoxic and ischemic heart and blood vessels, which may also contribute to cardiovascular pathology. The differential cellular and regional expression of ACE and chymase in the human heart and blood vessels suggests distinct pathophysiologic roles for these two A II-forming enzymes. The study of different pathways involved in tissue A II formation, including that of ACE- and chymase-independent enzymes, will clarify their respective contribution to the pathophysiologic changes in cardiovascular diseases, and help in planning a more comprehensive clinical strategy. This report reviews the properties of human heart chymase, an A II-forming serine proteinase, and compares it with those of ACE.