Taylor Peter C, Sivakumar Bran
The Kennedy Institute of Rheumatology, Division Imperial College Faculty of Medicine, London, UK.
Curr Opin Rheumatol. 2005 May;17(3):293-8. doi: 10.1097/01.bor.0000155361.83990.5b.
Angiogenesis is a prominent feature of rheumatoid synovitis. Although new blood vessels deliver oxygen to the augmented inflammatory cell mass, the neovascular network is dysfunctional and fails to restore tissue oxygen homeostasis, so that the rheumatoid joint remains a markedly hypoxic environment. The purpose of this review is to discuss the role of hypoxia and angiogenesis in the pathogenesis of rheumatoid arthritis.
Vascular pathologic change, in the form of angiogenesis, is important in the perpetuation of rheumatoid arthritis and, in the form of endothelial dysfunction, contributes to associated cardiovascular comorbidity. Recent data suggest that tumor necrosis factor-alpha blockade may modify the vascular pathologic changes in rheumatoid arthritis. Angiogenesis is a prominent feature of rheumatoid synovitis. Emerging evidence based on ultrasonographic vascular imaging and angiogenic biomarkers implicates angiogenesis in the active phase of erosive disease. Many factors contribute to the profoundly hypoxic environment that can arise within the joint affected by rheumatoid arthritis. At a cellular level, hypoxia is detected by a mechanism that regulates cytoplasmic concentrations of hypoxia-inducible factor-1alpha. After translocation to the nucleus, hypoxia-inducible factor-1alpha binds its partner hypoxia-inducible factor-1beta to form a heterodimeric, functional transcription factor, hypoxia-inducible factor-1, which activates a gene program associated with angiogenesis, glycolysis, and adaptation to pH.
Despite the luxuriant vasculature associated with rheumatoid arthritis synovitis, the joint affected by rheumatoid arthritis is hypoxic. Repetitive cycles of hypoxia and reoxygenation together with oxidants produced by phagocytic cells promote chronic oxidative stress within the microenvironment of the affected joint, leading to the generation of reactive oxygen species with the potential to contribute to tissue damage.
血管生成是类风湿性滑膜炎的一个显著特征。尽管新血管为增加的炎症细胞团提供氧气，但新生血管网络功能失调，无法恢复组织氧稳态，因此类风湿关节仍处于明显缺氧的环境中。本综述的目的是讨论缺氧和血管生成在类风湿关节炎发病机制中的作用。
血管生成形式的血管病理变化在类风湿关节炎的持续发展中很重要，而内皮功能障碍形式的血管病理变化则导致相关的心血管合并症。最近的数据表明，肿瘤坏死因子-α 阻断可能会改变类风湿关节炎的血管病理变化。血管生成是类风湿性滑膜炎的一个显著特征。基于超声血管成像和血管生成生物标志物的新证据表明血管生成与侵蚀性疾病的活动期有关。许多因素导致类风湿关节炎受累关节内出现严重缺氧的环境。在细胞水平上，缺氧是通过一种调节缺氧诱导因子-1α 细胞质浓度的机制来检测的。转移到细胞核后，缺氧诱导因子-1α 与其伴侣缺氧诱导因子-1β 结合形成异二聚体功能性转录因子缺氧诱导因子-1，该因子激活与血管生成、糖酵解和pH适应相关的基因程序。
尽管类风湿关节炎滑膜炎伴有丰富的脉管系统，但类风湿关节炎受累关节仍处于缺氧状态。缺氧和复氧的重复循环以及吞噬细胞产生的氧化剂会在受累关节的微环境中促进慢性氧化应激，导致活性氧的产生，这可能会导致组织损伤。
