Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca2+-ATPase in a rat model of heart failure
Improvement in survival and cardiac metabolism after gene transfer of sarcoplasmic reticulum Ca2+-ATPase in a rat model of heart failure
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DOI：
10.1161/hc3601.095574
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发表时间：
2001-09-18
期刊：
影响因子：
37.8
通讯作者：
Hajjar, RJ
中科院分区：
文献类型：
--
作者：
del Monte, F;Williams, E;Hajjar, RJ
背景 - 在心力衰竭中，肌浆网（SR）Ca2 + -ATP酶（SERCA2a）活性降低，导致钙处理异常和收缩功能障碍。我们先前已经表明，通过基因转移增加SERCA2a的表达可改善由升主动脉缩窄所创建的心力衰竭大鼠模型的心室功能。
方法和结果 - 在本研究中，我们测试了SERCA2a基因转移对生存、左心室（LV）容积和代谢的影响。在主动脉缩窄后26至27周，所有动物都出现了心力衰竭（通过缩短分数降低>25％来证明），并随机使用基于导管的技术接受携带SERCA2a基因的腺病毒（Ad.SERCA2a）或对照病毒（Ad.β - 半乳糖苷酶 - 绿色荧光蛋白，Ad.β gal - GFP）。假手术大鼠，未感染或感染Ad.β gal - GFP或Ad.SERCA2a的，作为对照。基因转移4周后，用Ad.β gal - GFP治疗的心力衰竭大鼠的存活率为9％，而接受Ad.SERCA2a的大鼠为63％。心力衰竭时左心室容积显著增加（0.64 ± 0.05对0.35 ± 0.03 mL，P <...（此处原文似乎不完整）
Background-In heart failure, sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) activity is decreased, resulting in abnormal calcium handling and contractile dysfunction. We have previously shown that increasing SERCA2a expression by gene transfer improves ventricular function in a rat model of heart failure created by ascending aortic constriction.Methods and Results-In this study, we tested the effects of gene transfer of SERCA2a on survival, left ventricular (LV) volumes, and metabolism. By 26 to 27 weeks after aortic banding, all animals developed heart failure (as documented by > 25% decrease in fractional shortening) and were randomized to receive either an adenovirus carrying the SERCA2a gene (Ad.SERCA2a) or control virus (Ad.beta gal-GFP) by use of a catheter-based technique. Sham-operated rats, uninfected or infected with either Ad.beta gal-GFP or Ad.SERCA2a, served as controls. Four weeks after gene transfer, survival in rats with heart failure treated with Ad.beta gal-GFP was 9%, compared with 63% in rats receiving Ad.SERCA2a. LV volumes were significantly increased in heart failure (0.64 +/-0.05 versus 0.35 +/-0.03 mL, P