title: Angiotensin-(1-7) attenuated long-term hypoxia-stimulated cardiomyocyte apoptosis by inhibiting HIF-1α nuclear translocation via Mas receptor regulation.
abstract: Extreme hypoxia often leads to myocardial apoptosis and causes heart failure. Angiotensin-(1-7)Ang-(1-7) is well known for its cardio-protective effects. However, the effects of Ang-(1-7) on long-term hypoxia (LTH)-induced apoptosis remain unknown. In this study, we found that Ang-(1-7) reduced myocardial apoptosis caused by hypoxia through the Mas receptor. Activation of the Ang-(1-7)/Mas axis down-regulated the hypoxia pro-apoptotic signaling cascade by decreasing the protein levels of hypoxia-inducible factor 1α (HIF-1α) and insulin-like growth factor binding protein-3 (IGFBP3). Moreover, the Ang-(1-7)/Mas axis further inhibited HIF-1α nuclear translocation. On the other hand, Ang-(1-7) activated the IGF1R/PI3K/Akt signaling pathways, which mediate cell survival. However, the above effects were abolished by A779 treatment or silencing of Mas expression. Taken together, our findings indicate that the Ang-(1-7)/Mas axis protects cardiomyocytes from LTH-stimulated apoptosis. The protective effect of Ang-(1-7) is associated with the inhibition of HIF-1α nuclear translocation and the induction of IGF1R and Akt phosphorylation.
authors.affiliation: a Graduate Institute of Basic Medical Science, China Medical University , Taichung , Taiwan .|b College of Chinese Medicine, School of Post-Baccalaureate Chinese Medicine, China Medical University , Taichung , Taiwan .
authors.forename: Ruey-Lin
authors.initials: RL
authors.lastname: Chang
authors.affiliation: a Graduate Institute of Basic Medical Science, China Medical University , Taichung , Taiwan .
authors.forename: Jing-Wei
authors.initials: JW
authors.lastname: Lin
authors.affiliation: c Department of Biological Science and Technology , China Medical University , Taichung , Taiwan .
authors.forename: Wei-Wen
authors.initials: WW
authors.lastname: Kuo
authors.affiliation: d School of Medical Laboratory and Biotechnology, Chung Shan Medical University , Taichung , Taiwan .
authors.forename: Dennis Jine-Yuan
authors.initials: DJ
authors.lastname: Hsieh
authors.affiliation: e Department of Pathology , Changhua Christian Hospital , Changhua , Taiwan .|f en-Teh Junior College of Medicine, Nursing and Management , Miaoli , Taiwan .
authors.forename: Yu-Lan
authors.initials: YL
authors.lastname: Yeh
authors.affiliation: g Department of Nursing , Mei Ho University , Pingguang Road , Pingtung , Taiwan .
authors.forename: Chia-Yao
authors.initials: CY
authors.lastname: Shen
authors.affiliation: g Department of Nursing , Mei Ho University , Pingguang Road , Pingtung , Taiwan .
authors.forename: Cecilia-Hsuan
authors.initials: CH
authors.lastname: Day
authors.affiliation: h Chinese Medicine Department, China Medical University Beigang Hospital , Taichung , Taiwan .
authors.forename: Tsung-Jung
authors.initials: TJ
authors.lastname: Ho
authors.affiliation: i Department of Biotechnology , Bharathiar University , Coimbatore , India .
authors.forename: Vijaya Padma
authors.initials: VP
authors.lastname: Viswanadha
authors.affiliation: a Graduate Institute of Basic Medical Science, China Medical University , Taichung , Taiwan .|j Graduate Institute of Chinese Medical Science, China Medical University , Taichung , Taiwan , and.|k Department of Health and Nutrition Biotechnology , Asia University , Taichung , Taiwan.
authors.forename: Chih-Yang
authors.initials: CY
authors.lastname: Huang
mesh_terms: D021581:Active Transport, Cell Nucleus / Q000187:drug effects; D000803:Angiotensin I / Q000494:pharmacology*; D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D015687:Cell Hypoxia; D002467:Cell Nucleus / Q000378:metabolism; D002478:Cells, Cultured; D051795:Hypoxia-Inducible Factor 1, alpha Subunit / Q000378:metabolism*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D010446:Peptide Fragments / Q000494:pharmacology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D044140:Receptor, Angiotensin, Type 1 / Q000378:metabolism*
chemical_list: C497444:Hif1a protein, rat; D051795:Hypoxia-Inducible Factor 1, alpha Subunit; D010446:Peptide Fragments; D044140:Receptor, Angiotensin, Type 1; D000803:Angiotensin I; C118790:angiotensin I (1-7)
keywords: Ang-(1-7); HIF-1α; Mas; cardiomyocyte; long-term hypoxia; myocardial apoptosis