Summary

The vasculature plays a central role in human IBD, as studies have demonstrated an altered microvascular anatomy in the chronically inflamed bowel, which corresponds with altered immunologic function and vascular physiology. Microvascular dysfunction in IBD results in diminished perfusion capacity, which is linked to impaired wound healing and may contribute to the refractory mucosal damage that characterizes IBD. Only areas of the microvascular anatomy characterized by extensive remodeling from chronic inflammation and damage correlate with impaired vasoperfusion, as well as enhanced leukocyte interaction and sustained endothelial activation. Thus, we believe that the vasculature contributes to the initiation and perpetuation of chronic intestinal inflammation in IBD. Improved understanding of the vascular contribution in IBD pathogenesis will pave the way for the development of novel strategies targeting inflammatory and ischemic mechanisms, specifically endothelium-leukocyte interaction with antiadhesion molecule biologic agents and vasodilatory compounds to improve wound healing in areas of refractory mucosal ulceration.

Glossary

Crohn's disease: An inflammatory disease of the gastrointestinal tract whose etiopathogenesis is linked to a combination of both genetic and environmental causes. The peak incidence of onset occurs between 15 and 25 years of age, and a second peak is associated with the sixth decade of life. Common symptoms include recurrent abdominal pain, fatigue, fever, nausea, vomiting, weight loss and diarrhea. Complications include anemia, intestinal blockage from strictures, fistulas and anal fissures. Treatments target inflammation and include 5-aminosalicylate compounds, corticos-teroids, immunomodulators and anti-TNFalpha agents. Surgery is frequently needed to ameliorate complications of this life-long disease.

HIMEC (human intestinal microvascular endothelial cells): acronym for human small and large intestine specific in vitro endothelial cell lines.

Inflammatory bowel disease: The group of chronic inflammatory disorders involving the gastrointestinal tract, most commonly associated with ulcerative colitis and Crohn's disease.

MAdCAM-1: Mucosal cell adhesion molecule 1 is a member of the immunoglobulin gene superfamily, and this cell surface glycoprotein is expressed on specific vascular beds in the gastrointestinal mucosa, pancreas and brain. MAdCAM-1 is increased during inflammatory bowel disease, and is the endothelial ligand for leukocytes bearing the alpha4 beta 7 inte-grin, mediating selective leukocyte recruitment into tissues.

Microvascular dysfunction: is the physiologic disturbance or impairment of normal endothelial vasorelaxation in response to mediators such as acetylcholine. Microvascular dysfunction has been associated with coronary artery disease, hypercholesterolemia, diabetis mellitus and inflammatory bowel disease.

Ulcerative colitis: One of the inflammatory bowel diseases, characterized by peak onset during adolescence and early adulthood, with exclusive involvement of the large intestine. Disease invariably involves the anorec-tum, and will extend proximally in specific patient subgroups, involving the entire colon in approximately one-third of individuals. Treatment is focused on 5-aminosalicylates, corticosteroids and immunomodulator agents. A high percentage of patients (approximately one-third) will ultimately require total abdominal colectomy due to refractory inflammation or high propensity for malignant transformation.

References

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16. Hatoum, O. A., Binion, D. G., Otterson, M. F., and Gutterman, D. D. (2003). Acquired microvascular dysfunction in inflammatory bowel disease: Loss of nitric oxide-mediated vasodilation. Gastroenterology 125, 58-69. This article demonstrates a loss of nitric oxide mediated vasodilation is an acquired component of microvascular dysfunction in chronically inflamed microvessels isolated from resected CD and UC intestinal segments. Microvascular dysfunction was not identified in acute inflammation, nor was it seen in areas of uninvolved IBD intestine.

Capsule Biography

Ossama A. Hatoum, M.D., M.Sc., is a colorectal surgeon and Research Associate in the Division of Cardiovascular Medicine at the Medical College of Wisconsin, in Milwaukee, Wisconsin. His laboratory investigation focuses on mechanisms of vasodilator response in the human intestinal microcirculation in health and IBD.

David G. Binion, M.D., is Director of the IBD Center and Associate Professor of Medicine at the Medical College of Wisconsin, in Milwaukee, Wisconsin. His laboratory has focused on the vascular biology of chronic intestinal inflammation in human inflammatory bowel disease (IBD), with a special emphasis on endothelium-leukocyte interaction. His clinical work as a gastroenterologist is focused on the development of experimental therapy for patients with Crohn's disease and ulcerative colitis.

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