Zhang Jing, Ding Liang, Zhao Yannan, Sun Wenjie, Chen Bing, Lin Hang, Wang Xia, Zhang Lujie, Xu Biao, Dai Jianwu
Key Laboratory of Molecular Developmental Biology, Institute of Genetics and Developmental Biology, Chinese Academy of Sciences, Beijing, China.
Circulation. 2009 Apr 7;119(13):1776-84. doi: 10.1161/CIRCULATIONAHA.108.800565. Epub 2009 Mar 23.
Vascular endothelial growth factor (VEGF) is an important active protein for the induction of angiogenesis and improvement in cardiac function after myocardial ischemia; however, the lack of a delivery system targeted to the injured myocardium reduces the local therapeutic efficacy of VEGF and increases its possible adverse effects.
We produced a fusion protein (CBD-VEGF) consisting of VEGF and a collagen-binding domain (CBD). The fusion protein specifically bound to type I collagen in vitro. In addition, CBD-VEGF promoted human umbilical vein endothelial cell proliferation after binding to collagen, which indicates that it retained both growth factor activity and collagen-binding ability. When implanted subcutaneously in rats, collagen membranes loaded with CBD-VEGF were significantly vascularized. After it was injected into rats with acute myocardial infarction, CBD-VEGF was largely retained in the cardiac extracellular matrix, in which collagen I was rich. Four weeks after VEGF or CBD-VEGF was injected into the infarct border zone, cardiac function detected by echocardiography and hemodynamics was preserved in the CBD-VEGF group. Administration of CBD-VEGF also induced reduction of scar size, whereas native VEGF did not have these effects. In addition, a significant increase in the number of capillary vessels in infarcted hearts was found in the CBD-VEGF group.
The injection of CBD-VEGF improved cardiac function in rats with induced acute myocardial infarction. This could potentially provide a new treatment option for myocardial infarction.
血管内皮生长因子（VEGF）是诱导血管生成及改善心肌缺血后心脏功能的一种重要活性蛋白；然而，缺乏靶向损伤心肌的递送系统会降低VEGF的局部治疗效果，并增加其可能的不良反应。
我们制备了一种由VEGF和胶原结合域（CBD）组成的融合蛋白（CBD-VEGF）。该融合蛋白在体外能特异性结合I型胶原。此外，CBD-VEGF在与胶原结合后可促进人脐静脉内皮细胞增殖，这表明它同时保留了生长因子活性和胶原结合能力。将负载CBD-VEGF的胶原膜皮下植入大鼠后，其血管化程度显著提高。将CBD-VEGF注入急性心肌梗死大鼠体内后，它主要保留在富含I型胶原的心脏细胞外基质中。在将VEGF或CBD-VEGF注入梗死边缘区四周后，通过超声心动图和血流动力学检测发现，CBD-VEGF组的心脏功能得以保留。给予CBD-VEGF还能使瘢痕大小减小，而天然VEGF则无这些作用。此外，在CBD-VEGF组中，梗死心脏中的毛细血管数量显著增加。
注射CBD-VEGF可改善诱导性急性心肌梗死大鼠的心脏功能。这可能为心肌梗死提供一种新的治疗选择。
