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European Journal of Heart Failure 2008 10(1):47-54; doi:10.1016/j.ejheart.2007.10.013
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© 2008 European Society of Cardiology

rAAV-asPLB transfer attenuates abnormal sarcoplasmic reticulum Ca2+-ATPase activity and cardiac dysfunction in rats with myocardial infarction

Xiao-Yan Zhaoa, Shen-Jiang Hua,c,*, Jiang Lia, Yun Moua, Ka Bianb,c, Jian Suna and Zhao-Hui Zhua

a Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University 79 Qingchun Road, Hangzhou 310003, China
b Department of Integrative Biology and Pharmacology, The University of Texas-Houston Medical School 6431 Fannin, Houston, TX, 77030, USA
c E-Institute of Shanghai Universities, Division of Nitric Oxide and Inflammatory Medicine China

* Corresponding author. Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China. Tel.: +86 571 87236569; fax: 86 571 87236628. E-mail address: s0hu0001{at}hotmail.com


   Abstract

Background: Diminished myocardial sarcoplasmic reticulum Ca2+-ATPase (SERCA) activity and upregulated phospholamban (PLB) level during cardiac dysfunction, had been reported in many studies.

Aims: The current study was designed to examine the effects of rAAV-antisense phospholamban (asPLB) gene transfer on cardiac function, SERCA expression and activity, as well as PLB expression and phosphorylation (Pser16-PLB), in a rat myocardial infarction (MI) model.

Methods and results: Rat MI model was generated by ligating the left anterior descending coronary artery. Four weeks later, left ventricular ejection fraction (LVEF), left ventricular systolic pressure (LVSP), the maximal rates of increase and decrease in intraventricular pressure (±dp/dtmax) were significantly depressed, and left ventricular end diastolic pressure (LVEDP) was increased. Myocardial PLB was markedly increased while both SERCA activity and Pser16-PLB level were decreased. In rAAV-asPLB transfected rats, rAAV-asPLB, which was injected into the myocardium around the infarction area immediately after the coronary artery ligation, effectively attenuated the depression of cardiac function, significantly inhibited the expression of PLB, restored Pser16-PLB level and enhanced myocardium SERCA activity.

Conclusion: rAAV-asPLB transfer in rats with MI effectively prevented the progression of heart failure.

Key Words: Heart failure • Gene therapy • RNA, antisense

Received February 15, 2007; Revised August 22, 2007; Accepted October 19, 2007


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