title: Homocysteine induces cardiac hypertrophy by up-regulating ATP7a expression.
abstract: OBJECTIVE
  The aim of the study is to investigate the molecular mechanism by which homocysteine (Hcy) induces cardiac hypertrophy.
  
  
  METHODS
  Primary cardiomyocytes were obtained from baby Sprague-Dawley rats within 3 days after birth. Flow cytometry was used to measure cell sizes. Quantitative real-time polymerase chain reaction was performed to measure the expression of β-myosin heavy chain and atrial natriuretic peptide genes. Western blotting assay was employed to determine ATP7a protein expression. Cytochrome C oxidase (COX) activity test was used to evaluate the activity of COX. Atomic absorption spectroscopy was performed to determine copper content. siRNAs were used to target-silence the expression of ATP7a.
  
  
  RESULTS
  Hcy induced cardiac hypertrophy and increased the expression of cardiac hypertrophy-related genes. ATP7a was a key factor in cardiac hypertrophy induced by Hcy. Reduced ATP7a expression inhibited cardiac hypertrophy induced by Hcy. Elevated ATP7a expression induced by Hcy inhibited COX activity. Enhanced ATP7a expression inhibited COX activity by lowering intracellular copper content.
  
  
  CONCLUSIONS
  Hcy elevates ATP7a protein expression, reduces copper content, and lowers COX activity, finally leading to cardiac hypertrophy.
authors.affiliation: Department of Cardiology, General Hospital of Pingmei Shenma Medical Group Pingdingshan 467000, P.R. China.
authors.forename: Zhanwei
authors.initials: Z
authors.lastname: Cao
authors.affiliation: Department of Cardiology, First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, P.R. China.
authors.forename: Yanzhou
authors.initials: Y
authors.lastname: Zhang
authors.affiliation: Critical Care Medical Department, First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, P.R. China.
authors.forename: Tongwen
authors.initials: T
authors.lastname: Sun
authors.affiliation: Critical Care Medical Department, First Affiliated Hospital of Zhengzhou University Zhengzhou 450000, P.R. China.
authors.forename: Shuguang
authors.initials: S
authors.lastname: Zhang
authors.affiliation: Department of Cardiology, General Hospital of Pingmei Shenma Medical Group Pingdingshan 467000, P.R. China.
authors.forename: Weiya
authors.initials: W
authors.lastname: Yu
authors.affiliation: Department of Intervention, Pingdingshan City First People's Hospital Pingdingshan 467000, P.R. China.
authors.forename: Jie
authors.initials: J
authors.lastname: Zhu
mesh_terms: D000251:Adenosine Triphosphatases / Q000378:metabolism*; D000818:Animals; D006332:Cardiomegaly / Q000235:genetics / Q000378:metabolism*; D027682:Cation Transport Proteins / Q000378:metabolism*; D049108:Cell Enlargement / Q000187:drug effects*; D003300:Copper / Q000378:metabolism; D000073840:Copper-Transporting ATPases; D003576:Electron Transport Complex IV / Q000378:metabolism; D006710:Homocysteine / Q000494:pharmacology*; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D015854:Up-Regulation / Q000187:drug effects*; D024723:Ventricular Myosins / Q000235:genetics / Q000378:metabolism
chemical_list: D027682:Cation Transport Proteins; D006710:Homocysteine; D003300:Copper; D003576:Electron Transport Complex IV; D000251:Adenosine Triphosphatases; D024723:Ventricular Myosins; C486202:Atp7a protein, rat; D000073840:Copper-Transporting ATPases
keywords: ATP7a; Homocysteine; cardiac hypertrophy; copper content; cytochrome C oxidase