Angiogenesis in Inflammatory Bowel Disease

Abstract

Angiogenesis is an important component of pathogenesis of inflammatory bowel disease (IBD). Chronic inflammation and angiogenesis are two closely related processes. Chronic intestinal inflammation is dependent on angiogenesis and this angiogenesis is modulated by immune system in IBD. Angiogenesis is a very complex process which includes multiple cell types, growth factors, cytokines, adhesion molecules, and signal transduction. Lymphangiogenesis is a new research area in the pathogenesis of IBD. While angiogenesis supports inflammation via leukocyte migration, carrying oxygen and nutrients, on the other hand, it has a major role in wound healing. Angiogenic molecules look like perfect targets for the treatment of IBD, but they have risk for serious side effects because of their nature.

Figure 1

Stages of angiogenesis process. (a) Normal, quiescent intestinal vessel: endothelial cells (ECs) with smooth basal membrane and regular extracellular matrix (ECM) are seen. (b) After angiogenic stimulation, activated EC secretes various proangiogenic and proinflammatory molecules. Then, increased permeability, vasodilatation, and extravasation of leucocytes occur. Basal membrane and ECM are degraded by metalloproteinases and proteases. ECs proliferate and migrate from this degraded area. After sprouting, ECs adhere to the matrix. (c) Tubulogenesis, lumen formation, and beginning of stabilization. (d) Remodeling and maturation: angiogenesis is completed in this stage by migration of pericytes and vascular smooth muscle cells to this area. If maturation of this new vessel is not completed, angiogenesis continues as pathogenic angiogenesis.

Figure 2

Relationship between bowel lumen, endothelium, immune cells, and vessel in immune-driven angiogenesis in inflammatory bowel disease. bFGF: basic fibroblast growth factor; Gro-1: growth-regulated oncogene-1; HGF: hepatocyte growth factor; IFN: interferon; IL: interleukin; MCP-1: monocyte chemoattractant protein; NO: nitric oxide; PDGF: platelet-derived growth factor; PG: prostaglandin; ROS: reactive oxygen species; TGF: transforming growth factor; TNF: tumor necrosis factor; VEGF: vascular endothelial growth factor.