Angiogenesis in Inflammatory Bowel Disease

The etiology of inflammatory bowel disease (IBD) is not precisely defined. However, it involves environmental factors, genetic predisposition, the involvement of gut microbiota, and abnormal immune response. Angiogenesis seems to be an integral part of IBD. Impairment of the intestinal barrier may represent an initiating or early feature of the disease. Disruption of the epithelial barrier leads to the translocation of microbiota and other antigens into the mucosa, resulting in an enhanced immune response, whereas damage to the vascular barrier is related to endothelial activation and pathologic angiogenesis, both of which promote inflammation. Angiogenesis during IBD is a very complex phenomenon that includes endothelial and immune cells, growth factors, cytokines, adhesion molecules, intestinal microbiota, and signal transduction. It seems that intestinal microvascular hemostasis shifts toward a prothrombotic state, and microthrombi formation exacerbates ischemia. The angiogenic process in IBD is regulated, at least in part, by the intestinal microbiota. Antiangiogenic therapy represents a novel and significant approach to the treatment of IBD. Biologic anti-inflammatory therapy for IBD simultaneously attenuates angiogenesis to a similar degree. However, the expression of VEGF and other growth factors may have dual and opposing effects, probably depending on the stage of the disease. Thus, anti-angiogenic treatment in patients with IBD remains controversial, and clinical trials of anti-angiogenic agents are warranted.