ACE2/ANG-(1-7)/Mas pathway in the brain: the axis of good

Am J Physiol Regul Integr Comp Physiol. 2011 Apr;300(4):R804-17. doi: 10.1152/ajpregu.00222.2010. Epub 2010 Dec 22.


The last decade has seen the discovery of several new components of the renin-angiotensin system (RAS). Among them, angiotensin converting enzyme-2 (ACE2) and the Mas receptor have forced a reevaluation of the original cascade and led to the emergence of a new arm of the RAS: the ACE2/ANG-(1-7)/Mas axis. Accordingly, the new system is now seen as a balance between a provasoconstrictor, profibrotic, progrowth axis (ACE/ANG-II/AT(1) receptor) and a provasodilatory, antifibrotic, antigrowth arm (ACE2/ANG-(1-7)/Mas receptor). Already, this simplistic vision is evolving and new components are branching out upstream [ANG-(1-12) and (pro)renin receptor] and downstream (angiotensin-IV and other angiotensin peptides) of the classical cascade. In this review, we will summarize the role of the ACE2/ANG-(1-7)/Mas receptor, focusing on the central nervous system with respect to cardiovascular diseases such as hypertension, chronic heart failure, and stroke, as well as neurological diseases. In addition, we will discuss the new pharmacological (antagonists, agonists, activators) and genomic (knockout and transgenic animals) tools that are currently available. Finally, we will review the latest data regarding the various signaling pathways downstream of the Mas receptor.

Publication types

  • Research Support, N.I.H., Extramural
  • Review

MeSH terms

  • Angiotensin I / physiology*
  • Angiotensin-Converting Enzyme 2
  • Animals
  • Brain / physiology*
  • Humans
  • Mice
  • Models, Animal
  • Peptide Fragments / physiology*
  • Peptidyl-Dipeptidase A / physiology*
  • Proto-Oncogene Proteins / physiology
  • Rats
  • Receptors, G-Protein-Coupled / physiology
  • Renin-Angiotensin System / physiology
  • Signal Transduction / physiology


  • Peptide Fragments
  • Proto-Oncogene Proteins
  • Receptors, G-Protein-Coupled
  • proto-oncogene proteins c-mas-1
  • Angiotensin I
  • Peptidyl-Dipeptidase A
  • ACE2 protein, human
  • Ace2 protein, mouse
  • Ace2 protein, rat
  • Angiotensin-Converting Enzyme 2
  • angiotensin I (1-7)