Angiotensin-(1-7) attenuates angiotensin II-induced cardiac hypertrophy via a Sirt3-dependent mechanism

The objectives of the present study were to investigate the effect of ANG-(1–7) on the development of cardiac hypertrophy and to identify the intracellular mechanism underlying this action of ANG-(1–7). Blood pressure and heart rate were recorded using radiotelemetry before and after chronic subcutaneous infusion of control (PBS), ANG II, ANG-(1–7), or ANG II + ANG-(1–7) for 4 wk in normotensive rats. Chronic administration of ANG-(1–7) did not affect either basal blood pressure or the ANG II-induced elevation in blood pressure. However, ANG-(1–7) significantly attenuated ANG II-induced cardiac hypertrophy and perivascular fibrosis in these rats. These effects of ANG-(1–7) were confirmed in cultured cardiomyocytes, in which ANG-(1–7) significantly attenuated ANG II-induced increases in cell size. This protective effect of ANG-(1–7) was significantly attenuated by pretreatment with A779 (a Mas receptor antagonist) or Mito-TEMPO (a mitochondria-targeting superoxide scavenger) as well as blockade of Sirt3 (a deacetylation-acting protein) by viral vector-mediated overexpression of sirtuin (Sirt)3 short hairpin (sh)RNA. Western blot analysis demonstrated that treatment with ANG-(1–7) dramatically increased Sirt3 expression. In addition, ANG-(1–7) attenuated the ANG II-induced increase in mitochondrial ROS generation, an effect that was abolished by A779 or Sirt3 shRNA. Moreover, ANG-(1–7) increased FoxO3a deac...
Source: AJP: Heart and Circulatory Physiology - Category: Cardiology Authors: Tags: RESEARCH ARTICLE Source Type: research