Angiotensin-(1–7) attenuates angiotensin II-induced cardiac hypertrophy via a Sirt3-dependent mechanism
| العنوان: | Angiotensin-(1–7) attenuates angiotensin II-induced cardiac hypertrophy via a Sirt3-dependent mechanism |
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| المؤلفون: | Stephen T. O'Rourke, Tiecheng Zhong, Chengwen Sun, Qi Zhang, Lirong Guo, Ankang Yin |
| المصدر: | American Journal of Physiology-Heart and Circulatory Physiology. 312:H980-H991 |
| بيانات النشر: | American Physiological Society, 2017. |
| سنة النشر: | 2017 |
| مصطلحات موضوعية: | Male, 0301 basic medicine, medicine.medical_specialty, Cardiotonic Agents, SIRT3, Physiology, Cardiomegaly, 030204 cardiovascular system & hematology, Muscle hypertrophy, Rats, Sprague-Dawley, Angiotensin Receptor Antagonists, 03 medical and health sciences, 0302 clinical medicine, Fibrosis, Physiology (medical), Internal medicine, medicine, Animals, Sirtuins, Myocytes, Cardiac, Cell Size, Angiotensin 1, Superoxide Dismutase, Mechanism (biology), business.industry, Angiotensin II, medicine.disease, Peptide Fragments, Rats, 030104 developmental biology, Endocrinology, Blood pressure, Cardiac hypertrophy, cardiovascular system, Angiotensin I, Reactive Oxygen Species, Cardiology and Cardiovascular Medicine, business, hormones, hormone substitutes, and hormone antagonists, Signal Transduction |
| الوصف: | 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 deacetylation and SOD2 expression, and these effects were blocked by Sirt3 shRNA. In summary, the protective effects of ANG-(1–7) on ANG II-induced cardiac hypertrophy and increased mitochondrial ROS production are mediated by elevated SOD2 expression via stimulation of Sirt3-dependent deacetylation of FoxO3a in cardiomyocytes. Thus, activation of the ANG-(1–7)/Sirt3 signaling pathway could be a novel therapeutic strategy in the management of cardiac hypertrophy and associated complications. NEW & NOTEWORTHY Chronic subcutaneous ANG-(1–7) has no effect on ANG II-induced elevations in blood pressure but significantly attenuates ANG II-induced cardiac hypertrophy and fibrosis by a mitochondrial ROS-dependent mechanism. This protective effect of ANG-(1–7) against the action of ANG II action is mediated by stimulation of sirtuin-3-mediated deacetylation of FoxO3a, which triggers SOD2 expression. |
| تدمد: | 1522-1539 0363-6135 |
| الوصول الحر: | https://explore.openaire.eu/search/publication?articleId=doi_dedup___::24ddaa1cbb8b8bb8b92f7ceb149065f9Test https://doi.org/10.1152/ajpheart.00768.2016Test |
| حقوق: | OPEN |
| رقم الانضمام: | edsair.doi.dedup.....24ddaa1cbb8b8bb8b92f7ceb149065f9 |
| قاعدة البيانات: | OpenAIRE |
| تدمد: | 15221539 03636135 |
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