Counter- regulatory renin–angiotensin system in cardiovascular disease

Abstract

The renin–angiotensin system is an important component of the cardiovascular system. Mounting evidence suggests that the metabolic products of angiotensin I and II — initially thought to be biologically inactive — have key roles in cardiovascular physiology and pathophysiology. This non- canonical axis of the renin–angiotensin system consists of angiotensin 1–7 , angiotensin 1–9, angiotensin- converting enzyme 2, the type 2 angiotensin II receptor (AT2R), the proto- oncogene Mas receptor and the Mas- related G protein- coupled receptor member D. Each of these components has been shown to counteract the effects of the classical renin– angiotensin system. This counter- regulatory renin–angiotensin system has a central role in the pathogenesis and development of various cardiovascular diseases and, therefore, represents a potential therapeutic target. In this Review , we provide the latest insights into the complexity and interplay of the components of the non- canonical renin–angiotensin system, and discuss the function and therapeutic potential of targeting this system to treat cardiovascular disease.