Jelkmann W
Institut für Physiologie, Medizinische Universität zu Lübeck, Ratzeburger Allee 160, D-23538 Lübeck, Germany.
Clin Chem. 2001 Apr;47(4):617-23.
Vascular endothelial growth factor (VEGF) is a protein with antiapoptotic, mitogenic, and permeability-increasing activities specific for vascular endothelium. VEGF mRNA, which has five isoforms, is produced by nonmalignant cells in response to hypoxia and inflammation and by tumor cells in constitutively high concentrations. Because VEGF plays a crucial role in physiological and pathophysiological angiogenesis, measurements of circulating VEGF are of diagnostic and prognostic value, e.g., in cardiovascular failures, inflammatory diseases, and malignancies. However, there are major quantitative differences in the published results. This review attempts to identify reasons for these disparities.
The literature was reviewed through a Medline search covering 1995 to 2000. A selection of exemplary references had to be made for this perspective overview.
Data are included from studies on healthy humans, gynecological patients, and persons suffering from inflammatory or malignant diseases. The results indicate that competitive immunoassays detect the total amount of circulating VEGF, which enables observations regarding the increase in VEGF in pregnancy and preeclampsia to be made. In these cases, capture immunoassays utilizing neutralizing antibodies are insufficient because of an accompanying increase in VEGF-binding soluble receptors (sFlt-1). Measurements of circulating free VEGF are useful for study of malignant diseases, which are associated with both genetically and hypoxia-induced overproduction of VEGF. The VEGF isoform specificity of the antibodies is also critical because both VEGF(121) and VEGF(165) are secreted. It is important to consider that platelets and leukocytes release VEGF during blood clotting.
Future efforts should concentrate on the balance between free VEGF, total VEGF, and sFlt-1. Plasma, rather than serum, should be used for analysis.
血管内皮生长因子（VEGF）是一种对血管内皮具有抗凋亡、促有丝分裂和增加通透性活性的蛋白质。VEGF mRNA有五种异构体，由非恶性细胞在缺氧和炎症反应时产生，也由肿瘤细胞以持续高浓度产生。由于VEGF在生理和病理生理血管生成中起关键作用，循环VEGF的测量具有诊断和预后价值，例如在心血管衰竭、炎症性疾病和恶性肿瘤中。然而，已发表的结果存在重大的数量差异。本综述试图找出这些差异的原因。
通过检索1995年至2000年的Medline数据库对文献进行综述。为了进行这一视角概述，必须挑选一些示例性参考文献。
数据包括对健康人、妇科患者以及患有炎症或恶性疾病者的研究。结果表明，竞争性免疫测定法可检测循环VEGF的总量，这使得能够观察到妊娠和先兆子痫时VEGF的增加。在这些情况下，由于伴随VEGF结合可溶性受体（sFlt-1）增加，利用中和抗体的捕获免疫测定法是不够的。循环游离VEGF的测量对研究恶性疾病有用，恶性疾病与VEGF的基因和缺氧诱导的过量产生有关。抗体的VEGF异构体特异性也很关键，因为VEGF(121)和VEGF(165)都会分泌。重要的是要考虑到血小板和白细胞在血液凝固过程中会释放VEGF。
未来的工作应集中在游离VEGF、总VEGF和sFlt-1之间的平衡上。分析应使用血浆而非血清。
