title: Improved cardiac function after sarcoplasmic reticulum Ca(2+)-ATPase gene transfer in a heart failure model induced by chronic myocardial ischaemia.
abstract: OBJECTIVE
  Chronic myocardial ischaemia (CMI) has become an important cause of heart failure (HF). The aim of this study was to examine the effects of sarco-endoplasmic reticulum calcium ATPase (SERCA2a) gene transfer in large HF animal models induced by CMI.
  
  
  RESULTS
  HF was induced in mini pigs by proximal left anterior descending coronary (LAD) ameroid constrictors. After confirmation of myocardial perfusion defects and cardiac function impairment, animals were divided into 4 groups (each including 4 animals): the HF group; the HF+enhanced green fluorescent protein (EGFP) group; the HF+SERCA2a group; and sham animals as a control group, rAAV1-EGFP and rAAV1-SERCA2a were injected intramyocardially to animals of the HF+EGFP and HF+SERCA2a groups separately. Sixty days after gene transfer, expressions of SERCA2a were examined, cardiac functions and changes of serum inflammatory and neuro-hormonal factors were determined. The results demonstrated that 60 days after gene transfer, LVEF, Ev/Av and +/- dp/dtmax of the HF+SERCA2a group increased significantly (P < 0.05), along with an increase in SERCA2a protein expression (P < 0.05) compared with the HF/HF+EGFP groups. Serum concentrations of inflammatory and neuro-hormonal factors were also decreased in the HF+SERCA2a group (P < 0.05).
  
  
  CONCLUSIONS
  Restoration of SERCA2a in myocardium of HF model induced by CMI could significantly improve cardiac function, suggesting its potential therapeutic significance in CMI-related heart failure.
authors: First Department of Geriatric Cardiology, Chinese PLA General Hospital, Beijing, China.
authors: Wei
authors: W
authors: Xin
authors: Xiaoying
authors: X
authors: Li
authors: Xiaochun
authors: X
authors: Lu
authors: Kun
authors: K
authors: Niu
authors: Jimei
authors: J
authors: Cai
mesh_terms: D000256:Adenoviridae / Q000235:genetics; D000804:Angiotensin II / Q000097:blood; D000818:Animals; D004195:Disease Models, Animal; D019332:Endothelin-1 / Q000097:blood; D005456:Fluorescent Dyes; D018014:Gene Transfer Techniques; D015316:Genetic Therapy; D049452:Green Fluorescent Proteins; D006333:Heart Failure / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D015850:Interleukin-6 / Q000097:blood; D008297:Male; D009203:Myocardial Infarction / Q000150:complications; D009206:Myocardium / Q000378:metabolism; D020097:Natriuretic Peptide, Brain / Q000097:blood; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics* / Q000378:metabolism; D013318:Stroke Volume; D013552:Swine; D013556:Swine, Miniature; D014409:Tumor Necrosis Factor-alpha / Q000097:blood
chemical_list: D019332:Endothelin-1; D005456:Fluorescent Dyes; D015850:Interleukin-6; D014409:Tumor Necrosis Factor-alpha; C485184:enhanced green fluorescent protein; D000804:Angiotensin II; D020097:Natriuretic Peptide, Brain; D049452:Green Fluorescent Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases