Battegay E J
Department of Research and Internal Medicine, University Hospital, Basel, Switzerland.
J Mol Med (Berl). 1995 Jul;73(7):333-46. doi: 10.1007/BF00192885.
This review of angiogenesis aims to describe (a) stimuli that either elicit or antagonize angiogenesis, (b) the response of the vasculature to angiogenic or anti-angiogenic stimuli, i.e., processes required for the formation of new vessels, (c) aspects of angiogenesis relating to tissue remodeling and disease, and (d) the potential of angiogenic or antiangiogenic therapeutic measures. Angiogenesis, the formation of new vessels from existing microvessels, is important in embryogenesis, wound healing, diabetic retinopathy, tumor growth, and other diseases. Hypoxia and other as yet ill-defined stimuli drive tumor, inflammatory, and connective tissue cells to generate angiogenic molecules such as vascular endothelial growth factor (VEGF), fibroblast growth factor (FGF), transforming growth factor-beta (TGF-beta), platelet-derived growth factor (PDGF), and others. Natural and synthetic angiogenesis inhibitors such as angiostatin and thalidomide can repress angiogenesis. Angiogenic and antiangiogenic molecules control the formation of new vessels via different mechanisms. VEGF and FGF elicit their effects mainly via direct action on relevant endothelial cells. TGF-beta and PDGF can attract inflammatory or connective tissue cells which in turn control angiogenesis. Additionally, PDGF may act differently on specific phenotypes of endothelial cells that are engaged in angiogenesis or that are of microvascular origin. Thus phenotypic traits of endothelial cells committed to angiogenesis may determine their cellular responses to given stimuli. Processes necessary for new vessel formation and regulated by angiogenic/antiangiogenic molecules include the migration and proliferation of endothelial cells from the microvasculature, the controlled expression of proteolytic enzymes, the breakdown and reassembly of extracellular matrix, and the morphogenic process of endothelial tube formation. In animal models some angiogenesis-dependent diseases can be controlled via induction or inhibition of new vessel formation. Life-threatening infantile hemangiomas are a first established indication for antiangiogenic therapy in humans. Treatment of other diseases by modulation of angiogenesis are currently tested in clinical trials. Thus the manipulation of new vessel formation in angiogenesis-dependent conditions such as wound healing, inflammatory diseases, ischemic heart and peripheral vascular disease, myocardial infarction, diabetic retinopathy, and cancer is likely to create new therapeutic options.
（a）引发或拮抗血管生成的刺激因素；（b）脉管系统对血管生成或抗血管生成刺激的反应，即新血管形成所需的过程；（c）与组织重塑和疾病相关的血管生成方面；（d）血管生成或抗血管生成治疗措施的潜力。血管生成，即从现有微血管形成新血管，在胚胎发育、伤口愈合、糖尿病视网膜病变、肿瘤生长及其他疾病中都很重要。缺氧和其他尚未明确的刺激因素促使肿瘤细胞、炎症细胞和结缔组织细胞生成血管生成分子，如血管内皮生长因子（VEGF）、成纤维细胞生长因子（FGF）、转化生长因子-β（TGF-β）、血小板衍生生长因子（PDGF）等。天然和合成的血管生成抑制剂，如血管抑素和沙利度胺，可抑制血管生成。血管生成和抗血管生成分子通过不同机制控制新血管的形成。VEGF和FGF主要通过直接作用于相关内皮细胞发挥作用。TGF-β和PDGF可吸引炎症或结缔组织细胞，进而控制血管生成。此外，PDGF对参与血管生成或源自微血管的内皮细胞的特定表型可能有不同作用。因此，致力于血管生成的内皮细胞的表型特征可能决定其对特定刺激因素的细胞反应。由血管生成/抗血管生成分子调节的新血管形成所需过程包括微血管内皮细胞的迁移和增殖、蛋白水解酶的受控表达、细胞外基质的分解和重组以及内皮管形成的形态发生过程。在动物模型中，一些依赖血管生成的疾病可通过诱导或抑制新血管形成来控制。危及生命的婴儿血管瘤是人类抗血管生成治疗首个已确立的适应证。目前正在临床试验中测试通过调节血管生成治疗其他疾病。因此，在依赖血管生成的情况下，如伤口愈合、炎症性疾病、缺血性心脏病和外周血管疾病、心肌梗死、糖尿病视网膜病变和癌症中，操纵新血管形成可能会创造新的治疗选择。
