Peacock D J, Banquerigo M L, Brahn E
Department of Medicine, UCLA School of Medicine 90024.
J Exp Med. 1992 Apr 1;175(4):1135-8. doi: 10.1084/jem.175.4.1135.
Neovascularization is observed in a spectrum of diseases such as solid tumors, diabetic retinopathy, and rheumatoid arthritis. It is also evident in rat collage-induced arthritis (CIA), an animal model with histologic, clinical, and radiographic manifestations resembling rheumatoid arthritis. To evaluate the effects of angioinhibition in CIA, Louvain rats were immunized with type II collagen to induce arthritis and then administered an angiogenesis inhibitor, AGM-1470, in an attempt to either prevent arthritis or suppress established disease. Using clinical and radiographic criteria, AGM-1470 prevented CIA and significantly suppressed established disease without evidence of immunosuppression. Histologic sections from control ankle joints manifested pannus and neovascularization, which were absent in experimental animals. This is the first study to investigate this novel agent in an autoimmune disease, and additional evaluation of this promising compound in other diseases that are potentially angiogenesis dependent, such as rheumatoid arthritis, might be warranted.
在一系列疾病中都可观察到新生血管形成,如实体瘤、糖尿病视网膜病变和类风湿关节炎。在大鼠胶原诱导性关节炎(CIA)中也很明显,这是一种动物模型,其组织学、临床和影像学表现类似于类风湿关节炎。为了评估血管抑制在CIA中的作用,用II型胶原免疫鲁汶大鼠以诱导关节炎,然后给予血管生成抑制剂AGM - 1470,试图预防关节炎或抑制已有的疾病。根据临床和影像学标准,AGM - 1470预防了CIA并显著抑制了已有的疾病,且没有免疫抑制的证据。对照踝关节的组织学切片显示有血管翳和新生血管形成,而实验动物中则没有。这是第一项在自身免疫性疾病中研究这种新型药物的研究,可能有必要对这种有前景的化合物在其他可能依赖血管生成的疾病(如类风湿关节炎)中进行进一步评估。