tailieunhanh - Báo cáo sinh học: "SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice"

SERCA2a gene transfer improves electrocardiographic Tuyển tập báo cáo các nghiên cứu khoa học quốc tế ngành hóa học dành cho các bạn yêu hóa học tham khảo đề tài: performance in aged mdx mice | Shin et al. Journal of Translational Medicine 2011 9 132 http content 9 1 132 JOURNAL OF TRANSLATIONAL MEDICINE RESEARCH Open Access SERCA2a gene transfer improves electrocardiographic performance in aged mdx mice Jin-Hong Shin1 Brian Bostick1 Yongping Yue1 Roger Hajjar2 and Dongsheng Duan1 Abstract Background Cardiomyocyte calcium overloading has been implicated in the pathogenesis of Duchenne muscular dystrophy DMD heart disease. The cardiac isoform of sarcoplasmic reticulum calcium ATPase SERCA2a plays a major role in removing cytosolic calcium during heart muscle relaxation. Here we tested the hypothesis that SERCA2a over-expression may mitigate electrocardiography ECG abnormalities in old female mdx mice a murine model of DMD cardiomyopathy. Methods 1 X 1012 viral genome particles mouse of adeno-associated virus serotype-9 AAV-9 SERCA2a vector was delivered to 12-m-old female mdx mice N 5 via a single bolus tail vein injection. AAV transduction and the ECG profile were examined eight months later. Results The vector genome was detected in the hearts of all AAV-injected mdx mice. Immunofluorescence staining and western blot confirmed SERCA2a over-expression in the mdx heart. Untreated mdx mice showed characteristic tachycardia PR interval reduction and QT interval prolongation. AAV-9 SERCA2a treatment corrected these ECG abnormalities. Conclusions Our results suggest that AAV SERCA2a therapy may hold great promise in treating dystrophindeficient heart disease. Background The heart is often afflicted in Duchenne muscular dystrophy DMD a lethal muscle disease caused by dystrophin deficiency reviewed in 1 . Dystrophin is a large sub-sarcolemmal protein that plays a critical role in maintaining sarcolemma integrity. In a dystrophin-deficient heart myocardial contraction results in sarcolem-mal damage. Subsequent cardiomyocyte necrosis and fibrosis leads to dilated cardiomyopathy. The exact molecular mechanisms underlying .