Multiple Pathogenic Roles of Microvasculature in Inflammatory Bowel Disease: A Jack of All Trades

Abstract

The etiology of Crohn's disease and ulcerative colitis, the two major forms of inflammatory bowel disease (IBD), is still largely unknown. However, it is now clear that the abnormalities underlying pathogenesis of intestinal inflammation are not restricted to those mediated by classic immune cells but also involve nonimmune cells. In particular, advances in vascular biology have outlined a central and multifaceted pathogenic role for the microcirculation in the initiation and perpetuation of IBD. The microcirculation and its endothelial lining play a crucial role in mucosal immune homeostasis through tight regulation of the nature and magnitude of leukocyte migration from the intravascular to the interstitial space. Chronically inflamed IBD microvessels display significant alterations in microvascular physiology and function compared with vessels from healthy and uninvolved IBD intestine. The investigation into human IBD has demonstrated how endothelial activation present in chronically inflamed IBD microvessels results in a functional phenotype that also includes leakiness, chemokine and cytokine expression, procoagulant activity, and angiogenesis. This review contemplates the newly uncovered contribution of intestinal microcirculation to pathogenesis and maintenance of chronic intestinal inflammation. In particular, we assess the multiple roles of the microvascular endothelium in innate immunity, leukocyte recruitment, coagulation and perfusion, and immune-driven angiogenesis in IBD.

Anti-microbial antibodies in celiac disease: Trick or treat?

“…The known predisposing factors for bacterial translocation, such as bacterial overgrowth in the small bowel (secondary to intestinal dysmotility) [41][42][43] , the damage to the integrity of the gut Papp M et al . Antibodies in celiac disease mucosa (secondary to alterations of the local intestinal microvasculature) [44,45] , which results in reduced oxygen delivery and an increased formation in oxygen radicals [46] as well as the upregulation of the proinflammatory cytokines, such as tumor necrosis factor α, interleukin-17 or interferon gamma in active lesions [47] , and the defective mucosal immunological defense [21,48] are all typical features in both clinical conditions. The significance of the enhanced bacterial translocation out of the small bowel in the anti-microbial antibody formation is further supported by the fact that the presence of the serological response among patients with Crohn's disease is mainly characteristic for those with complicated (stricturing or penetrating) small bowel involvement and is rarely observed in the isolated colonic disease or in patients with ulcerative colitis.…”

A computational approach to compare microvessel distributions in tumors following antiangiogenic treatments

“…Provided the availability of suitable mouse models, these investigations might involve Crohn's disease, 33,34 ulcerative colitis, or other inflammatory bowel pathologies. 35,36 These future fields of investigation raise questions about the speed of analysis. Morphological dilation is a slow process, therefore a more efficient approach to compute the permeation curves would use the Euclidean Distance Map of the non-vessel fraction of the images.…”

Id1 Expression in Endothelial Cells of the Colon Is Required for Normal Response to Injury

“…4,33,34 Several proangiogenic factors, including vascular endothelial growth factor (VEGF), IL-8, PGE 2 , and fibroblast growth factor have been shown to be overexpressed in Crohn disease and ulcerative colitis. However, the significance of ID1, a proangiogenic inhibitory transcription factor in regulating endothelial function, in IBD has not been studied.…”