title: Aldehyde dehydrogenase 2 deficiency blunts compensatory cardiac hypertrophy through modulating Akt phosphorylation early after transverse aorta constriction in mice.
abstract: This study was designed to examine the impact of mitochondrial aldehyde dehydrogenase 2 (ALDH2) on transverse aorta constriction (TAC)-induced cardiac hypertrophy and related molecular mechanisms using an ALDH2 knockout (ALDH2-/-) murine model.
  
  
  
  Male wild-type and ALDH2-/- mice were subjected to TAC or sham operation (n=6-8 for each group). After two weeks, cardiac function was assessed by echocardiography and hemodynamic measurements. Myocardial phosphorylated and total PI3K, the catalytic subunit of PI3Ks (p110α and p110γ), Akt, and total PTEN levels were detected by Western blotting. Cardiomyocytes were stretched for 6h in vitro in the presence or absence of Alda-1 (a small-molecule activator of ALDH2) prior to assessment of phosphorylated PI3K, Akt and total PTEN expressions by Western blot.
  
  
  
  Heart to body weight ratio and left ventricular posterior wall thickness as well as the cross-sectional area of cardiomyocyte were significantly lower in ALDH2-/- mice than in wild-type mice following TAC. Western blot analysis showed p110γ was upregulated post TAC in both wild-type mice and ALDH2-/- mice, phosphorylation of Akt was disrupted, PTEN expression was upregulated in ALDH2-/- mice post TAC while phosphorylated PI3K, p110α and p110γ expression was similar between ALDH2-/- and wild-type mice post TAC. In vitro, phosphorylation of Akt was significantly accentuated and PTEN expression was reduced while PI3K phosphorylation remained unchanged in stretched cardiomyocytes pretreated by Alda-1 compared to stretched cardiomyocytes treated by saline.
  
  
  
  Our results show that ALDH2 deficiency attenuates compensatory cardiac hypertrophy through regulating Akt but not PI3K phosphorylation early after TAC in mice.
authors.affiliation: Department of Cardiology, Shanghai East Hospital, Tongji University, Shanghai 200120, PR China.
authors.forename: Guang
authors.initials: G
authors.lastname: Xia
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Fan
authors.initials: F
authors.lastname: Fan
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Ming
authors.initials: M
authors.lastname: Liu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Shijun
authors.initials: S
authors.lastname: Wang
authors.affiliation: Institute of Biomedical Science, Fudan University, Shanghai 200032, PR China.
authors.forename: Jian
authors.initials: J
authors.lastname: Wu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Cheng
authors.initials: C
authors.lastname: Shen
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Shasha
authors.initials: S
authors.lastname: Han
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Cong
authors.initials: C
authors.lastname: Wang
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Jianguo
authors.initials: J
authors.lastname: Jia
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Institute of Biomedical Science, Fudan University, Shanghai 200032, PR China.
authors.forename: Yunzeng
authors.initials: Y
authors.lastname: Zou
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China.
authors.forename: Kai
authors.initials: K
authors.lastname: Hu
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Institute of Biomedical Science, Fudan University, Shanghai 200032, PR China. Electronic address: jbge@zs-hospital.sh.cn.
authors.forename: Junbo
authors.initials: J
authors.lastname: Ge
authors.affiliation: Shanghai Institute of Cardiovascular Diseases, Zhongshan Hospital, Fudan University, Shanghai 200032, PR China; Institute of Biomedical Science, Fudan University, Shanghai 200032, PR China. Electronic address: sun.aijun@zs-hospital.sh.cn.
authors.forename: Aijun
authors.initials: A
authors.lastname: Sun
mesh_terms: D000071396:Aldehyde Dehydrogenase, Mitochondrial / Q000172:deficiency* / Q000235:genetics; D000818:Animals; D001011:Aorta; D001549:Benzamides / Q000494:pharmacology; D052117:Benzodioxoles / Q000494:pharmacology; D006332:Cardiomegaly / Q000209:etiology* / Q000378:metabolism* / Q000473:pathology; D002478:Cells, Cultured; D003250:Constriction; D004195:Disease Models, Animal; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000378:metabolism; D051059:PTEN Phosphohydrolase / Q000378:metabolism; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism*
chemical_list: D001549:Benzamides; D052117:Benzodioxoles; C531525:N-(1,3-benzodioxol-5-ylmethyl)-2,6-dichlorobenzamide; C515029:ALDH2 protein, mouse; D000071396:Aldehyde Dehydrogenase, Mitochondrial; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D051059:PTEN Phosphohydrolase; C487757:Pten protein, mouse
keywords: ALDH2; Akt; Compensatory cardiac hypertrophy; PI3K; PTEN; Transverse aorta constriction