Elastin overexpression by cell-based gene therapy preserves matrix and prevents cardiac dilation.
Elastin overexpression by cell-based gene therapy preserves matrix and prevents cardiac dilation.
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DOI：
10.1111/j.1582-4934.2012.01560.x
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发表时间：
2012-10
影响因子：
5.3
通讯作者：
Li RK
中科院分区：
文献类型：
--
作者：
Li SH;Sun Z;Guo L;Han M;Wood MF;Ghosh N;Vitkin IA;Weisel RD;Li RK
心肌梗死后，纤维化瘢痕变薄和扩张导致进行性心力衰竭。弹性蛋白的损失是梗塞心脏的不利细胞外基质重塑的主要贡献者，并且梗塞区域的弹性性质的恢复可以防止心室功能障碍。我们植入基因修饰的细胞，使其过度表达弹性蛋白，以重建梗死心肌的弹性，防止心力衰竭。克隆人弹性蛋白全长cDNA，亚克隆入腺病毒载体，然后转导到大鼠骨髓基质细胞（BMSCs）中。体外研究表明，骨髓基质细胞表达弹性蛋白，并沉积到细胞外基质中。将转导的BMSCs注射到成年大鼠的梗死心肌中。对照组接受用绿色荧光蛋白基因转导的BMSC或单独的培养基。梗死心肌中弹性蛋白沉积与心肌组织结构完整性的保护相关（偏振光双折射;与对照组相比P < 0.05）。结果，梗死瘢痕厚度和舒张顺应性得以维持，并防止了梗死扩大（与对照组相比P < 0.05）。在9周的时间内，植入BMSCs的大鼠表现出比培养基对照更好的心脏功能;然而，接受过表达弹性蛋白的BMSCs的大鼠表现出最大的功能改善（P < 0.01）。弹性蛋白在梗死心脏中的过度表达保留了细胞外基质的弹性结构，这反过来又保留了舒张功能，防止心室扩张并保留了心脏功能。这种基于细胞的基因治疗为心脏再生提供了一种新的方法。
After a myocardial infarction, thinning and expansion of the fibrotic scar contribute to progressive heart failure. The loss of elastin is a major contributor to adverse extracellular matrix remodelling of the infarcted heart, and restoration of the elastic properties of the infarct region can prevent ventricular dysfunction. We implanted cells genetically modified to overexpress elastin to re-establish the elastic properties of the infarcted myocardium and prevent cardiac failure. A full-length human elastin cDNA was cloned, subcloned into an adenoviral vector and then transduced into rat bone marrow stromal cells (BMSCs). In vitro studies showed that BMSCs expressed the elastin protein, which was deposited into the extracellular matrix. Transduced BMSCs were injected into the infarcted myocardium of adult rats. Control groups received either BMSCs transduced with the green fluorescent protein gene or medium alone. Elastin deposition in the infarcted myocardium was associated with preservation of myocardial tissue structural integrity (by birefringence of polarized light; P < 0.05 versus controls). As a result, infarct scar thickness and diastolic compliance were maintained and infarct expansion was prevented (P < 0.05 versus controls). Over a 9-week period, rats implanted with BMSCs demonstrated better cardiac function than medium controls; however, rats receiving BMSCs overexpressing elastin showed the greatest functional improvement (P < 0.01). Overexpression of elastin in the infarcted heart preserved the elastic structure of the extracellular matrix, which, in turn, preserved diastolic function, prevented ventricular dilation and preserved cardiac function. This cell-based gene therapy provides a new approach to cardiac regeneration.
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亚蛛网膜下腔出血：与载脂蛋白E和弹性蛋白基因关联的测试。
影响因子：
--
作者：
Kaushal, Ritesh;Woo, Daniel;Pal, Prodipto;Haverbusch, Mary;Xi, Huifeng;Moomaw, Charles;Sekar, Padmini;Kissela, Brett;Kleindorfer, Dawn;Flaherty, Matthew;Sauerbeck, Laura;Chakraborty, Ranajit;Broderick, Joseph;Deka, Ranjan
通讯作者：
Deka, Ranjan
影响因子：
4.6
作者：
Fujii, T;Yau, TM;Li, RK
通讯作者：
Li, RK
影响因子：
2.8
作者：
Wilson, Brian C.;Vitkin, I. Alex;Matthews, Dennis L.
通讯作者：
Matthews, Dennis L.
DOI：
10.1152/ajpheart.00862.2004
发表时间：
2005-06-01
影响因子：
4.8
作者：
Mizuno, T;Mickle, DAG;Li, RK
通讯作者：
Li, RK
影响因子：
37.8
作者：
Mizuno, T;Yau, TM;Li, RK
通讯作者：
Li, RK