rAAV-asPLB transfer attenuates abnormal sarcoplasmic reticulum Ca2+ -ATPase activity and cardiac dysfunction in rats with myocardial infarction.
BACKGROUND
Diminished myocardial sarcoplasmic reticulum Ca(2+)-ATPase (SERCA) activity and upregulated phospholamban (PLB) level during cardiac dysfunction, had been reported in many studies.


OBJECTIVE
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.


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/dt(max)) 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.


CONCLUSIONS
rAAV-asPLB transfer in rats with MI effectively prevented the progression of heart failure.
Zhao
Xiao-Yan
XY
Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.
Hu
Shen-Jiang
SJ
Li
Jiang
J
Mou
Yun
Y
Bian
Ka
K
Sun
Jian
J
Zhu
Zhao-Hui
ZH
D000256:Adenoviridae / Q000235:genetics; D000818:Animals; D016375:Antisense Elements (Genetics) / Q000378:metabolism / Q000627:therapeutic use*; D002118:Calcium / Q000032:analysis / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D000252:Calcium-Transporting ATPases / Q000378:metabolism*; D018014:Gene Transfer Techniques; D005822:Genetic Vectors / Q000235:genetics / Q000627:therapeutic use; D006333:Heart Failure / Q000209:etiology / Q000628:therapy*; D008297:Male; D009203:Myocardial Infarction / Q000150:complications* / Q000201:enzymology / Q000473:pathology; D009206:Myocardium / Q000201:enzymology; D011897:Random Allocation; D051381:Rats; D017208:Rats, Wistar; D012519:Sarcoplasmic Reticulum / Q000201:enzymology*; D015996:Survival Rate; D000099211:Phospholamban
D016375:Antisense Elements (Genetics); D002118:Calcium; D002135:Calcium-Binding Proteins; D000252:Calcium-Transporting ATPases; D000099211:Phospholamban