Lewis B S, Flugelman M Y, Weisz A, Keren-Tal I, Schaper W
Department of Cardiology, Lady Davis Carmel Medical Center, Haifa, Israel.
Cardiovasc Res. 1997 Sep;35(3):490-7. doi: 10.1016/s0008-6363(97)00170-3.
The concept of therapeutic angiogenesis is based on the premise that the potential for vascular growth inherent in vascular tissue can be utilized to promote the development of new blood vessels under the influence of the appropriate growth factors. Direct application of growth factors of the fibroblast (acidic, basic fibroblast growth factor, FGF-5), endothelial (vascular endothelial growth factor) and other series has been effective in preliminary studies. Angiogenesis by gene transfer provides an attractive alternative, with the advantage that the protein may continue to be secreted for a longer period of time and that the gene may be targeted to specific tissues to enhance efficacy and reduce systemic side effects. Angiogenesis by gene transfer is currently under investigation using a variety of growth factors and a wide array of potential delivery systems. These include application of the gene as naked DNA or by viral vector in the proximal vessel by direct intravascular injection, interventional cardiologic techniques (hydrogel coating on balloon, double balloon system, stent implantation) or by direct application to adventitia, pericardium or ischemic tissue distal to the site of arterial obstruction. As our understanding of the molecular and genetic processes underlying angiogenesis increases, and as we examine the results of preliminary animal and human protocols, we hope to develop the potential of angiogenesis by gene transfer for therapeutic use.
治疗性血管生成的概念基于这样一个前提，即血管组织固有的血管生长潜力可在适当生长因子的影响下用于促进新血管的形成。在初步研究中，直接应用成纤维细胞生长因子（酸性、碱性成纤维细胞生长因子、FGF - 5）、内皮细胞生长因子（血管内皮生长因子）及其他系列生长因子已取得成效。通过基因转移实现血管生成提供了一种有吸引力的替代方法，其优点在于蛋白质可能会持续分泌更长时间，并且基因可以靶向特定组织以提高疗效并减少全身副作用。目前正在使用多种生长因子和一系列潜在的递送系统对通过基因转移实现血管生成进行研究。这些方法包括将基因作为裸DNA或通过病毒载体通过直接血管内注射应用于近端血管、介入性心脏技术（球囊上的水凝胶涂层、双球囊系统、支架植入），或直接应用于动脉阻塞部位远端的外膜、心包或缺血组织。随着我们对血管生成潜在分子和遗传过程的理解不断加深，以及我们对初步动物和人体实验方案结果的研究，我们希望开发通过基因转移实现血管生成的治疗应用潜力。
