Vascular Responses to Intestinal Inflammation

Abstract

The microcirculation both responds and contributes to an inflammatory response. The inflammatory bowel diseases (IBD) provide a useful example of the profound reactivity of all segments (arterioles, capillaries, venules) of the microvasculature to inflammation, and illustrate how changes in microvascular function can influence the intensity and progression of disease activity. This chapter describes the key alterations in gut microvascular function that accompany human and experimental IBD, and addresses the prevailing views on the cellular and molecular mechanisms that underlie the altered vascular function. Impaired blood flow regulation (impaired vasomotor function), an increased adhesion of leukocytes and platelets to the vessel wall, activation of the coagulation cascade, enhanced thrombus formation, increased vascular permeability, and an accelerated rate of vascular proliferation (angiogenesis) are characteristic features of the phenotypic changes that occur in the gut vasculature during inflammation. These changes have been linked to the activation of cells that normally circulate in blood (leukocytes, platelets) or reside in the vessel wall (endothelial cells, vascular smooth muscle) or in the perivascular space (macrophages, mast cells). The chemical messengers elaborated from these activated cells stimulate different signaling pathways that ultimately elicit the phenotypic microvascular responses that accompany inflammation. Pharmacological interventions directed towards preventing some of the microvascular alterations in inflammation (e.g., angiogenesis) provide novel and potentially effective targets for treatment of IBD.

D. Neil Granger and Norman R. Harris are supported by a grant from the National Institutes of Diabetes and Digestive and Kidney Diseases (P01 DK43785-19).