Role of the endothelium in inflammatory bowel diseases

Abstract

Inflammatory bowel diseases (IBD) are a complex group of diseases involving alterations in mucosal immunity and gastrointestinal physiology during both initiation and progressive phases of the disease. At the core of these alterations are endothelial cells, whose continual adjustments in structure and function coordinate vascular supply, immune cell emigration, and regulation of the tissue environment. Expansion of the endothelium in IBD (angiogenesis), mediated by inflammatory growth factors, cytokines and chemokines, is a hallmark of active gut disease and is closely related to disease severity. The endothelium in newly formed or inflamed vessels differs from that in normal vessels in the production of and response to inflammatory cytokines, growth factors, and adhesion molecules, altering coagulant capacity, barrier function and blood cell recruitment in injury. This review examines the roles of the endothelium in the initiation and propagation of IBD pathology and distinctive features of the intestinal endothelium contributing to these conditions.

Keywords: Adhesion molecules; Chemokines; Crohn’s disease; Cytokines; Endothelium; Growth factors; Inflammation; Microvasculature; Nitric oxide; Ulcerative colitis.

Figure 1

Inflammation triggers a change in the endothelium of the intestinal vasculature in response to the cytokines, chemokines and growth factors released by immune cells leading to increased angiogenesis, adhesion molecule expression, leukocyte extravasation, decreased endothelial barrier function and increased coagulation. TNF: Tumor necrosis factor; IL: Interleukin; iNOS: Inducible nitric oxide synthase; eNOS: Endothelial nitric oxide synthase; VEGF: Vascular endothelial growth factor; MMPs: Matrix metalloproteinases; VCAM: Vascular cell adhesive molecule; ICAM: Intracellular adhesive molecules.