IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
congresos y reuniones científicas
Título:
Exposure to GH induces a downregulation of the angiotensin-converting enzyme 2/angiotensin-(1-7)/Mas receptor axis in heart and kidney
Autor/es:
MUÑOZ MC; BURGHI V; MIQUET JG; MAZZIOTTA L; BANEGAS RD; DOMINICI FP
Lugar:
Belo Horizonte
Reunión:
Simposio; IX International Symposium Vasoactive Peptides; 2013
Resumen:
Acromegaly, a disease with onset in adult life as a consequence of chronic growth hormone (GH) production, leads to increased morbility and mortality mainly associated with cardiovascular and/or metabolic alterations. Cardiovascular and renal diseases are commonly associated with alterations of the GH/IGF-1 axis and involve an imbalance within the renin-angiotensin system (RAS). However, there is scant information available regarding the effects of disturbances in the GH/IGF-1 axis on the in vivo expression of the main components of the RAS. The RAS is conceived as a coordinated hormonal cascade involved in the control of cardiovascular, renal, and adrenal functions, mainly through the actions of angiotensin (Ang) II through two receptors, AT1R and AT2R. Activation of the AT1R, promotes vasoconstriction, reactive oxygen species production; extracellular matrix remodeling and inflammation response, tissue injury and IR. On the other hand, the AT2R inhibits cell growth, inflammation and fibrosis; and exerts a cardio-protective role against ischemia-reperfusion injury and acute myocardial infarction. Advances in the field led to the recognition of other active components of the RAS metabolism, such as Ang-(1-7), the ACE2, that forms Ang-(1-7) directly from Ang II and indirectly from Ang I, and the Ang-(1-7) specific receptor Mas. The ACE2/Ang-(1-7)/MasR axis in general opposes the vascular and proliferative effects of Ang II. Therefore, our hypothesis is that overexpression of GH in mice may display modifications on the expression of cardiac and renal main components of the RAS towards a negative status of this system that could explain at least in part their hypertension, cardiovascular and renal damage. We evaluated the levels of AT1R, AT2R and MasR, as well as ACE, ACE2 in the heart and the kidney of transgenic mice overexpressing bovine GH (PEPCK-bGH mice) by both immunohistochemistry and Western blotting analysis. We observed a decrease of the MasR and ACE2 in both tissues. Unexpectedly AT1R was reduced in heart and kidney of PEPCK-bGH mice. AT2R was decreased in the kidney and unaltered in the heart. ACE levels remained unaltered in the heart and the kidney of transgenic mice. The shift within the RAS towards an attenuation of the ACE2/Ang-(1-7)/Mas receptor axis observed in PEPCK-bGH mice may contribute to the increased incidence of hypertension and cardiovascular disfunction displayed by this animal model of acromegaly.