Freedman Saul Benedict, Isner Jeffrey M
Department of Cardiology, Concord Repatriation General Hospital, University of Sydney, Hospital Road, Concord, New South Wales 2139, Australia.
Ann Intern Med. 2002 Jan 1;136(1):54-71. doi: 10.7326/0003-4819-136-1-200201010-00011.
A large body of evidence in animal models of ischemia shows that administration of angiogenic growth factors, either as recombinant protein or by gene transfer, can augment nutrient perfusion through neovascularization. Many cytokines have angiogenic activity; those that have been best studied in animal models and clinical trials are vascular endothelial growth factor (VEGF) and fibroblast growth factor (FGF). Clinical trials of therapeutic angiogenesis in patients with end-stage coronary artery disease have shown increases in exercise time and reductions in anginal symptoms and have provided objective evidence of improved perfusion and left ventricular function. Larger-scale placebo-controlled trials have been limited to intracoronary and intravenous administration of recombinant protein and have not yet shown significant improvement in exercise time or angina compared with placebo. Larger-scale placebo-controlled studies of gene transfer are in progress. Clinical studies are required to determine the optimal dose, formulation, route of administration, and combinations of growth factors and the utility of adjunctive endothelial progenitor-cell or stem-cell supplementation, to provide safe and effective therapeutic myocardial angiogenesis. Determination of which growth factors or cells are required to optimize therapeutic neovascularization in an individual patient should be a goal of future research.
大量缺血动物模型的证据表明，给予血管生成生长因子，无论是作为重组蛋白还是通过基因转移，都可以通过新血管形成增加营养物质灌注。许多细胞因子具有血管生成活性；在动物模型和临床试验中研究得最充分的是血管内皮生长因子（VEGF）和成纤维细胞生长因子（FGF）。终末期冠状动脉疾病患者的治疗性血管生成临床试验显示运动时间增加、心绞痛症状减轻，并提供了灌注改善和左心室功能改善的客观证据。更大规模的安慰剂对照试验仅限于冠状动脉内和静脉内给予重组蛋白，与安慰剂相比，运动时间或心绞痛尚未显示出显著改善。基因转移的更大规模安慰剂对照研究正在进行中。需要进行临床研究以确定最佳剂量、制剂、给药途径、生长因子组合以及辅助内皮祖细胞或干细胞补充的效用，以提供安全有效的治疗性心肌血管生成。确定在个体患者中优化治疗性新血管形成所需的生长因子或细胞应是未来研究的目标。
