Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues

Abstract

Chidlow JH Jr, Shukla D, Grisham MB, Kevil CG. Pathogenic angiogenesis in IBD and experimental colitis: new ideas and therapeutic avenues. Am J Physiol Gastrointest Liver Physiol 293: G5-G18, 2007. First published April 26, 2007; doi:10.1152/ajpgi.00107.2007.-Angiogenesis is now understood to play a major role in the pathology of chronic inflammatory diseases and is indicated to exacerbate disease pathology. Recent evidence shows that angiogenesis is crucial during inflammatory bowel disease (IBD) and in experimental models of colitis. Examination of the relationship between angiogenesis and inflammation in experimental colitis shows that initiating factors for these responses simultaneously increase as disease progresses and correlate in magnitude. Recent studies show that inhibition of the inflammatory response attenuates angiogenesis to a similar degree and, importantly, that inhibition of angiogenesis does the same to inflammation. Recent data provide evidence that differential regulation of the angiogenic mediators involved in IBD-associated chronic inflammation is the root of this pathological angiogenesis. Many factors are involved in this phenomenon, including growth factors/cytokines, chemokines, adhesion molecules, integrins, matrix-associated molecules, and signaling targets. These factors are produced by various vascular, inflammatory, and immune cell types that are involved in IBD pathology. Moreover, recent studies provide evidence that antiangiogenic therapy is a novel and effective approach for IBD treatment. Here we review the role of pathological angiogenesis during IBD and experimental colitis and discuss the therapeutic avenues this recent knowledge has revealed. inflammation; T cells; growth factors; adhesion molecules; antiangiogenesis ANGIOGENESIS PLAYS AN IMPORTANT role in many chronic inflammatory diseases including but not limited to diabetic retinopathy, atherosclerosis, rheumatoid arthritis, hypercholesterolemia, and psoriasis. It has been suggested that the angiogenic components of these diseases contribute to and exacerbate disease conditions (26, 31). Recent findings, both clinical and experimental, indicate that angiogenesis also plays a crucial role in the inflammatory bowel diseases (IBD), consisting of Crohn's disease (CD) and ulcerative colitis (UC) (31,37,58,131,155). Development of new vasculature during chronic inflammation may play a negative "pathological" role by contributing to increased inflammatory responses due to dysfunctional new vessel architecture and increases in the recruitment of inflammatory cell types. Importantly, recent data have shown that angiogenic inhibition during chronic inflammatory diseases attenuates further inflammation and disease pathology (31, 37, 51). As such, expanding our knowledge of how pathological angiogenesis occurs during IBD will further our ability to treat patients with these diseases. IBD PathogenesisCD and UC are idiopathic inflammatory disorders of the intestine and/or colon in which patients suffer from rectal bleeding, severe...

Clinical relevance of circulating midkine in ulcerative colitis

“…Also, the recruitment of inflammatory cells secreting angiogenic factors indirectly supports angiogenesis (37). Accordingly, in the present study midkine increases corresponded with increasing concentrations of VEGF-A and PDGF-BB, the prominent angiogenic factors involved in the pathogenesis of IBD (38).…”

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.…”

Percent changes in mesenteric blood T-lymphocyte subsets in gilts induced by low-dose zearalenone-deoxynivalenol mycotoxin

“…Zwierzęta te okazały się użyteczne do badań podstawowych stanów chorobowych, takich jak: uszkodzenia niedokrwienno-reperfuzyjne, zaburzenia jelitowe tła stresowego czy zespołu jelita krótkiego (11). Świnie są również bardzo obiecującym gatunkiem w badaniach funkcji bariery jelitowej (12), badaniach biomateriałów czy wykorzystania dodatków paszowych lub spożywczych w celach prewencyjno--terapeutycznych (2).…”

“…W badaniach dotyczących wpływu stanu zapalnego na naczynia błony śluzowej stwierdzono poszerzenie przestrzeni pomiędzy komórkami endotelialnymi, jak również zwiększoną adherencję leukocytów, erytrocytów i płytek krwi do śródbłonka (21). W badaniach angiograficznych obrazujących zmiany w naczyniach jelitowych podczas wrzodzieją-cego zapalenia jelita grubego (UC -ulcerative colitis) stwierdzono też poszerzenie światła naczyń oraz ich nieregularny przebieg (2). Należy również zwrócić uwagę na oddziaływanie samej mikotoksyny na naczynia krwionośne.…”