Angiotensin-(1-7): Blood, Heart, and Blood Vessels

Abstract

In the past few years, there has been a growing interest in the heptapeptide Angiotensin(Ang)-(1-7), mainly because of its ability to counter regulate many of Ang II actions. Furthermore, heart and blood vessels are important target tissues for Ang-(1-7) formation and actions. The introduction of novel tools, such as the Ang-(1-7) antagonists, A-779 and D-pro7-Ang-(1-7), the Ang-(1-7) agonist AVE 0991, transgenic rats TGR(A-1-7)3292, and use of liposome-encapsulated Ang-(1-7) for evaluating the biochemical and functional role of Ang-(1-7), have produced a great impact in this field of research. Moreover, the recent identification of the Ang-(1-7)-forming enzyme ACE2 and of the Ang-(1-7) receptor Mas will allow important advances in our understanding of the physiological and pathological role of this peptide. In this review, we will discuss the current knowledge concerning the biological effects of Ang-(1-7) in the blood, heart, and blood vessels. In addition, we will highlight the possible applications of agonists of its receptor as therapeutic agents in cardiovascular and related diseases.

Vascular Relaxation, Antihypertensive Effect, and Cardioprotection of a Novel Peptide Agonist of the Mas Receptor

“…39 Infusion of CGEN-856S did not change HR in normotensive rats, whereas in SHRs only transient and dose-independent slight changes in HR were observed. The mechanism(s) of this selective effect in SHRs remain to be clarified.…”

“…The current therapy to block the activity of the RAS includes ACE inhibitors, AT 1 receptors antagonists, and direct renin inhibitors. The accumulating evidence that stimulation of the ACE2/Ang-(1-7)/Mas axis produces cardioprotection and antihypertensive effects 8,19,35,39 raises the possibility of development of a next generation of RAS-related drugs aimed to increase the activity of this axis. 34,41 The results presented here, using CGEN-856S, in addition to reinforcing the concept that Mas stimulation produces beneficial cardiovascular effects, illustrates the potential of this novel therapeutic strategy for treating cardiovascular diseases.…”

Angiotensin-Converting Enzyme 2 (ACE2) in Disease Pathogenesis

“…Whereas ACE cleaves AngI into AngII, 7,8 ACE2 cleaves a single residue from AngII to generate Ang1-7, 11 which has an opposing role to ACE by counterbalancing AT1R-mediated actions. 19 Because ACE2 is a major Ang1-7-forming enzyme, 20 its identification has added further support to the biological significance of Ang-1-7. 10,18,21 Of note, gene targeting of ACE results in spontaneous hypotension, reduced sperm function, and kidney malformation.…”

Cardiac Overexpression of Angiotensin Converting Enzyme 2 Protects the Heart From Ischemia-Induced Pathophysiology

“…4 Second, ACE2 expression is increased in the myocardium after coronary artery ligation (CAL), 5,6 in addition to an increase in activity in failing human hearts. [7][8][9] Third, the major product of ACE2, Ang(1-7), produces beneficial outcomes on cardiac function (ie, coronary perfusion, endothelial function, and contractility) 10,11 and attenuates development of HF postischemia. 11,12 Fourth, overexpression of ACE2 protects the heart from hypertension-induced cardiac pathophysiology (ie, hypertrophy and fibrosis) [12][13][14] and inhibits hypoxia-induced collagen production by cardiac fibroblasts.…”

“…[7][8][9] Third, the major product of ACE2, Ang(1-7), produces beneficial outcomes on cardiac function (ie, coronary perfusion, endothelial function, and contractility) 10,11 and attenuates development of HF postischemia. 11,12 Fourth, overexpression of ACE2 protects the heart from hypertension-induced cardiac pathophysiology (ie, hypertrophy and fibrosis) [12][13][14] and inhibits hypoxia-induced collagen production by cardiac fibroblasts. 15 Finally, Ang pathway inhibitors used in the treatment of MI increase ACE2 gene expression and attenuate ACE2 gene downregulation in the myocardium after CAL.…”