Morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy.
Morphological and physiological restorations of hereditary form of dilated cardiomyopathy by somatic gene therapy.
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通过体细胞基因疗法恢复遗传性扩张型心肌病的形态和生理学。
DOI：
10.1006/bbrc.2001.4962
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发表时间：
2001
影响因子：
3.1
通讯作者：
T. Toyo
中科院分区：
文献类型：
--
作者：
T. Kawada;A. Sakamoto;M. Nakazawa;M. Urabe;F. Masuda;C. Hemmi;Y. Wang;W. Shin;Y. Nakatsuru;H. Sato;K. Ozawa;T. Toyo
扩张型心肌病TO-2系仓鼠，δ-肌聚糖（SG）基因缺失，α-、β-、γ-和δ-SG蛋白均不表达，可用于开发难治性心力衰竭的潜在基因治疗。我们制备了含有正常delta-SG基因的重组腺相关病毒载体，并进行了体内实验。转染的心肌诱导转录本和转基因的稳健表达，持续动物预期寿命的2/3时期。免疫组化结果显示，在转染区40%的细胞中，不仅有delta-SG的表达，而且有其他三种SG的表达，并且转导后的心肌细胞直径正常化。血流动力学研究显示舒张指数（LVEDP、dP/dt（min）和CVP）优先改善。这些结果提供了第一个证据，即补充具有有效和持续转染能力的特定基因可以恢复遗传、形态和功能恶化。
TO-2 strain hamsters with dilated cardiomyopathy, gene deletion of delta-sarcoglycan (SG) and no expression of alpha-, beta-, gamma-, and delta-SG proteins are useful for developing the potential gene therapy of intractable heart failure. We prepared recombinant adeno-associated virus vector including normal delta-SG gene driven by CMV promoter and intramurally administered in vivo. The transfected myocardium induced robust expression of both transcript and transgene for 2/3 period of the animal's life expectancy. Immunostaining demonstrated reexpression of not only delta-SG but also other three SGs in 40% cells in the transfected region and normalization of the diameter of transduced cardiomyocytes. Hemodynamic study revealed preferential amelioration of the diastolic indices (LVEDP, the dP/dt(min) and CVP). These results provide the first evidence that supplementation of a specific gene with efficient and sustained transfection capability restores the genetic, morphological, and functional deteriorations.
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影响因子：
37.8
作者：
Li, DX;Tapscoft, T;Roberts, R
通讯作者：
Roberts, R
影响因子：
37.8
作者：
Svensson, EC;Marshall, DJ;Leiden, JM
通讯作者：
Leiden, JM
影响因子：
158.5
作者：
MICHELS, VV;MOLL, PP;TAZELAAR, HD
通讯作者：
TAZELAAR, HD
影响因子：
20.1
作者：
GWATHMEY, JK;COPELAS, L;MORGAN, JP
通讯作者：
MORGAN, JP