A systematic review to investigate whether Angiotensin-(1-7) is a promising therapeutic target in human heart failure

Abstract

Context. Heart failure (HF) is a common condition causing much morbidity and mortality despite major advances in pharmacological and device therapies. Preclinical data suggest a cardioprotective role of Angiotensin-(1-7) in animal models of HF. Objective. Perform a systematic review on the effects of Angiotensin-(1-7) on humans, focusing on HF. Results. 39 studies were included in the review (4 in human HF and (35) in non-HF patients). There is only one intervention study on 8 patients with human HF, using Angiotensin-(1-7), with forearm blood flow (FBF) as the endpoint. Angiotensin-(1-7) caused no significant effect on FBF in this HF study but caused vasodilation in 3 out of 4 non-HF studies. In one other non-HF study, Angiotensin-(1-7) infusion led to a significant increase in blood pressure in normal men; however, effects were <0.03% that of angiotensin II. Cardioprotective effects seen in non-HF studies include for instance beneficial actions against atherosclerosis and myocardial fibrosis. Conclusions. The main finding of our systematic review is that Angiotensin-(1-7) plays an important cardioprotective role in HF in animals and in patients without heart failure. More research is required to test the hypothesis that Angiotensin-(1-7) benefits patients with heart failure.

Figure 1

Demonstrating the relationship between Angiotensin I, Angiotensin II, Ang-(1-7), and the converting enzymes (ACE and ACE2).

Figure 2

Flow of studies through the review.