the Vasculature and Inflammatory Bowel Disease. Contribution to Pathogenesis and Clinical Pathology

Although the human inflammatory bowel diseases (IBDs), Crohn’s disease (CD), and ulcerative colitis (UC) are well-known inflammatory disorders that are characterized by progressive destructive inflammation in the gastrointestinal tract, their etiology and promulgating factors remain a mystery. Recently, vasculopathy is being implicated in these disease processes in an increasing number of studies. Chronically inflamed IBD microvessels have demonstrated significant alterations in microvascular physiology and function compared with vessels from healthy and uninvolved IBD intestine. The microcirculation and its endothelial lining play a central role in the initiation and perpetuation of the inflammatory process, and investigation into human IBD has demonstrated an important role for the endothelium in both normal mucosal immunity as well as the dysregulated chronic inflammation characterizing IBD. Chronically inflamed IBD microvessels demonstrate an enhanced capacity to adhere leukocytes after inflammatory activation and have alterations in selective leukocyte recruitment compared with uninvolved areas of bowel. In addition to the role of the vasculature in leukocyte recruitment, both forms of IBD are characterized by refractory mucosal damage and ulceration with an impaired capacity to heal. Previous work has demonstrated an abnormal, remodeled vascular architecture characterized by stenotic microvessels in chronically inflamed CD and UC lesions. This would suggest chronic ischemia in the IBD gut. Human in vivo investigation has demonstrated a significant decrease in mucosal intestinal microvascular perfusion in chronic IBD gut inflammation. Significantly impaired endothelial-dependent microvascular vasorelaxation in chronically inflamed CD and UC bowel has been defined recently. In this work we review the role of the microvasculature in human chronic intestinal inflammation in IBD, our present understanding of the vasculature in disease etiopathogenesis, and the emerging IBD therapies, target the vasculature.