rAAV-asPLB transfer attenuates abnormal sarcoplasmic reticulum Ca(2+)-ATPase activity and cardiac dysfunction in rats with myocardial infarction.

@article{citeulike:2160349, abstract = {BACKGROUND: Diminished myocardial sarcoplasmic reticulum Ca(2+)-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/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. CONCLUSION: rAAV-asPLB transfer in rats with MI effectively prevented the progression of heart failure.}, address = {Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China.}, author = {Zhao, Xiao-Yan Y. and Hu, Shen-Jiang J. and Li, Jiang and Mou, Yun and Bian, Ka and Sun, Jian and Zhu, Zhao-Hui H. }, citeulike-article-id = {2160349}, doi = {http://dx.doi.org/10.1016/j.ejheart.2007.10.013}, issn = {1388-9842}, journal = {Eur J Heart Fail}, keywords = {aav, chf, pln}, month = {December}, posted-at = {2007-12-23 01:21:51}, priority = {3}, title = {rAAV-asPLB transfer attenuates abnormal sarcoplasmic reticulum Ca(2+)-ATPase activity and cardiac dysfunction in rats with myocardial infarction.}, url = {http://dx.doi.org/10.1016/j.ejheart.2007.10.013}, year = {2007} }

TY - JOUR ID - citeulike:2160349 L3 - citeulike-article-id:2160349 TI - rAAV-asPLB transfer attenuates abnormal sarcoplasmic reticulum Ca(2+)-ATPase activity and cardiac dysfunction in rats with myocardial infarction. JF - Eur J Heart Fail AD - Institute of Cardiology, The First Affiliated Hospital, College of Medicine, Zhejiang University, 79 Qingchun Road, Hangzhou 310003, China. SN - 1388-9842 N2 - BACKGROUND: Diminished myocardial sarcoplasmic reticulum Ca(2+)-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/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. CONCLUSION: rAAV-asPLB transfer in rats with MI effectively prevented the progression of heart failure. KW - aav KW - chf KW - pln AU - Zhao, Xiao-Yan AU - Hu, Shen-Jiang AU - Li, Jiang AU - Mou, Yun AU - Bian, Ka AU - Sun, Jian AU - Zhu, Zhao-Hui PY - 2007/12/18/ UR - http://dx.doi.org/10.1016/j.ejheart.2007.10.013 ER -