Angiotensin-(1-7) and angiotensin-(1-9): function in cardiac and vascular remodelling

The RAS (renin angiotensin system) is integral to cardiovascular physiology; however, dysregulation of this system largely contributes to the pathophysiology of CVD (cardiovascular disease). It is well established that Angll (angiotensin II), the main effector of the RAS, engages the AT(1)R (angiotensin type 1 receptor) and promotes cell growth, proliferation, migration and oxidative stress, all processes which contribute to remodelling of the heart and vasculature, ultimately leading to the development and progression of various CVDs, including heart failure and atherosclerosis. The counter-regulatory axis of the RAS, which is centred on the actions of ACE2 (angiotensin-converting enzyme 2) and the resultant production of Ang-(1-7) [angiotensin-(1-7)] from Angll, antagonizes the actions of Angll via the receptor Mas, thereby providing a protective role in CVD. More recently, another ACE2 metabolite, Ang-(1-9) [angiotensin-(1-9)], has been reported to be a biologically active peptide within the counter-regulatory axis of the RAS. The present review will discuss the role of the counter-regulatory RAS peptides Ang-(1-7) and Ang-(1-9) in the cardiovascular system, with a focus on their effects in remodelling of the heart and vasculature.