ACE2: more of Ang-(1-7) or less Ang II?
OBJECTIVE
Previous concepts regarding the pathways involved in the generation of angiotensin II (Ang II) have been challenged by studies showing the existence of a peptide acting as an endogenous antagonist of Ang II. The discovery that angiotensin-(1-7) [Ang-(1-7)] opposes the pressor, proliferative, profibrotic, and prothrombotic actions mediated by Ang II has contributed to the realization that the renin-angiotensin system is composed of two opposing arms: the pressor arm constituted by the enzyme angiotensin-converting enzyme (ACE), Ang II as the product, and the Ang II type 1 (AT1) receptor as the main protein mediating the biological actions of Ang II; the second arm is composed of the monocarboxypeptidase angiotensin-converting enzyme 2 (ACE2), Ang-(1-7) produced through hydrolysis of Ang II, and the Mas receptor as the protein conveying the vasodilator, antiproliferative, antifibrotic, and antithrombotic effects of Ang-(1-7).


RESULTS
Experimental and clinical studies demonstrate a role for the Ang-(1-7)/ACE2/Mas axis in the evolution of hypertension, the regulation of renal function, and the progression of renal disease including diabetic nephropathy. Additional evidence suggests that a reduction in the expression and activity of this vasodepressor component may be a critical factor in mediating the progression of cardiovascular disease.


CONCLUSIONS
Further research on the contribution of the Ang-(1-7)/ACE2/Mas axis to cardiovascular pathology will lead to the development of new pharmacological approaches resulting in the design of molecular or genetic means to increase the expression of ACE2, allow for increased tissue levels of Ang-(1-7), or both.
Department of General Surgery, Wake Forest University School of Medicine, Winston Salem, North Carolina 27157, USA. cferrari@wfubmc.edu
Carlos M
CM
Ferrario
D000803:Angiotensin I / Q000502:physiology*; D000804:Angiotensin II / Q000502:physiology*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D006801:Humans; D006973:Hypertension / Q000209:etiology*; D010446:Peptide Fragments / Q000502:physiology*; D007703:Peptidyl-Dipeptidase A / Q000502:physiology*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000502:physiology; D043562:Receptors, G-Protein-Coupled / Q000502:physiology; D015398:Signal Transduction
D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)