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.

METHODS AND 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: Wei Xin, Xiaoying Li, Xiaochun Lu, Kun Niu, Jimei Cai
• Journal: Acta cardiologica (Acta Cardiol) Vol. 66 Issue 1 Pg. 57-64 (Feb 2011) ISSN: 0001-5385 [Print] England
• PMID: 21446381 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Endothelin-1
• Fluorescent Dyes
• Interleukin-6
• Tumor Necrosis Factor-alpha
• enhanced green fluorescent protein
• Angiotensin II
• Natriuretic Peptide, Brain
• Green Fluorescent Proteins
• Sarcoplasmic Reticulum Calcium-Transporting ATPases

Topics

• Adenoviridae (genetics)
• Angiotensin II (blood)
• Animals
• Disease Models, Animal
• Endothelin-1 (blood)
• Fluorescent Dyes
• Gene Transfer Techniques
• Genetic Therapy
• Green Fluorescent Proteins
• Heart Failure (etiology, physiopathology, therapy)
• Interleukin-6 (blood)
• Male
• Myocardial Infarction (complications)
• Myocardium (metabolism)
• Natriuretic Peptide, Brain (blood)
• Sarcoplasmic Reticulum Calcium-Transporting ATPases (genetics, metabolism)
• Stroke Volume
• Swine
• Swine, Miniature
• Tumor Necrosis Factor-alpha (blood)