ACE2 and vasoactive peptides: novel players in cardiovascular/renal remodeling and hypertension.
The renin-angiotensin system (RAS) is a key component of cardiovascular physiology and homeostasis due to its influence on the regulation of electrolyte balance, blood pressure, vascular tone and cardiovascular remodeling. Deregulation of this system contributes significantly to the pathophysiology of cardiovascular and renal diseases. Numerous studies have generated new perspectives about a noncanonical and protective RAS pathway that counteracts the proliferative and hypertensive effects of the classical angiotensin-converting enzyme (ACE)/angiotensin (Ang) II/angiotensin type 1 receptor (AT1R) axis. The key components of this pathway are ACE2 and its products, Ang-(1-7) and Ang-(1-9). These two vasoactive peptides act through the Mas receptor (MasR) and AT2R, respectively. The ACE2/Ang-(1-7)/MasR and ACE2/Ang-(1-9)/AT2R axes have opposite effects to those of the ACE/Ang II/AT1R axis, such as decreased proliferation and cardiovascular remodeling, increased production of nitric oxide and vasodilation. A novel peptide from the noncanonical pathway, alamandine, was recently identified in rats, mice and humans. This heptapeptide is generated by catalytic action of ACE2 on Ang A or through a decarboxylation reaction on Ang-(1-7). Alamandine produces the same effects as Ang-(1-7), such as vasodilation and prevention of fibrosis, by interacting with Mas-related GPCR, member D (MrgD). In this article, we review the key roles of ACE2 and the vasoactive peptides Ang-(1-7), Ang-(1-9) and alamandine as counter-regulators of the ACE-Ang II axis as well as the biological properties that allow them to regulate blood pressure and cardiovascular and renal remodeling.
Advanced Center for Chronic Diseases (ACCDiS), Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Quimicas y Farmaceuticas and Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Evelyn
E
Mendoza-Torres
Advanced Center for Chronic Diseases (ACCDiS), Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Quimicas y Farmaceuticas and Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Alejandra
A
Oyarzún
Advanced Center for Chronic Diseases (ACCDiS), Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Quimicas y Farmaceuticas and Facultad de Medicina, Universidad de Chile, Santiago, Chile.
David
D
Mondaca-Ruff
Advanced Center for Chronic Diseases (ACCDiS), Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Quimicas y Farmaceuticas and Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Andrés
A
Azocar
Advanced Center for Chronic Diseases (ACCDiS), Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile Division Enfermedades Cardiovasculares, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Pablo F
PF
Castro
Division Enfermedades Cardiovasculares, Facultad de Medicina, Pontificia Universidad Católica de Chile, Santiago, Chile.
Jorge E
JE
Jalil
Advanced Center for Chronic Diseases (ACCDiS), Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Quimicas y Farmaceuticas and Facultad de Medicina, Universidad de Chile, Santiago, Chile.
Mario
M
Chiong
Advanced Center for Chronic Diseases (ACCDiS), Centro de Estudios Moleculares de la Célula, Facultad de Ciencias Quimicas y Farmaceuticas and Facultad de Medicina, Universidad de Chile, Santiago, Chile Department of Internal Medicine (Cardiology Division), University of Texas Southwestern Medical Center, Dallas, Texas, USA.
Sergio
S
Lavandero
Advanced Center for Chronic Diseases(ACCDiS), Facultad de Medicina, PontificiaUniversidad Católica de Chile, Santiago, Chile.Division Enfermedades Cardiovasculares,Facultad de Medicina, Pontificia UniversidadCatólica de Chile, Santiago, Chile mocaran@med.puc.cl.
María Paz
MP
Ocaranza
D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism*; D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D001794:Blood Pressure / Q000502:physiology; D002318:Cardiovascular Diseases / Q000503:physiopathology; D006801:Humans; D006973:Hypertension / Q000503:physiopathology; D007674:Kidney Diseases / Q000503:physiopathology; D051379:Mice; D009842:Oligopeptides / Q000378:metabolism; D010446:Peptide Fragments / Q000378:metabolism; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D000090063:Proto-Oncogene Mas; D051381:Rats; D012084:Renin-Angiotensin System / Q000502:physiology*
C000715470:MAS1 protein, human; D009842:Oligopeptides; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; C581752:alamandine; C506331:angiotensin I (1-9); D000804:Angiotensin II; D000803:Angiotensin I; D007703:Peptidyl-Dipeptidase A; C000705307:ACE2 protein, human; C000705328:Ace2 protein, mouse; C000705329:Ace2 protein, rat; D000085962:Angiotensin-Converting Enzyme 2; C118790:angiotensin I (1-7)
ACE2; alamandine; angiotensin-(1-7); angiotensin-(1-9); blood vessels; heart; hypertension; kidney; renin–angiotensin system; tissue remodeling