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 AngII (angiotensin II), the main effector of the RAS, engages the AT1R (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 AngII, antagonizes the actions of AngII 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.

Regulation of cardiovascular remodeling by the counter-regulatory axis of the renin-angiotensin system.

The counter-regulatory axis of the renin-angiotensin system (RAS) is a novel therapeutic target in cardiovascular disease. Pathophysiological effects mediated via angiotensin II (Ang II) are well established in regulation of blood pressure, cardiac and vascular remodeling, and renal sodium handling, which lead to disorders such as hypertension and associated end-organ damage, atherosclerosis and heart failure. The counter-regulatory axis of the RAS is centered on the angiotensin-converting enzyme 2/angiotensin-1-7 (Ang-[1-7])/Mas receptor axis and has been shown to inhibit many detrimental phenotypes in cardiovascular disease. More recently, an alternative peptide, angiotensin-(1-9) (Ang-[1-9]), has been reported as a potential new member of this axis. This review will discuss the cardiovascular regulatory roles of Ang-(1-7) and Ang-(1-9) in the counter-regulatory axis of the RAS, and the potential for new therapeutic approaches in cardiovascular disease.