Saudi Journal of Gastroenterology
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Year : 2007  |  Volume : 13  |  Issue : 1  |  Page : 37-38
Angiogenesis and inflammatory bowel disease

Division of Gastroenterology, King Khalid University Hospital, Riyadh, Saudi Arabia

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Date of Submission19-Oct-2006
Date of Acceptance23-Dec-2006


Inflammatory bowel disease (IBD) has gained immense attention recently due primarily to increasing prevalence. The exact disease mechanism is still unknown. There is considerable evidence of interrelation between the mechanisms of angiogenesis and the chronic inflammation of IBD. This evidence was obtained from animal models of colitis and confirmed in human studies. Serum levels of vascular endothelial growth factor (VEGF) and basic fibroblast growth factor (b-FGF) have been found to be significantly higher in patients with IBD than in controls. In addition, it was found that these factors correlate well with disease activity and decrease with the use of steroids. Therefore pharmacological inhibition of angiogenesis has the potential to be a therapeutic strategy in IBD.

Keywords: Angiogenesis, inflammatory bowel disease

How to cite this article:
Azzam N. Angiogenesis and inflammatory bowel disease. Saudi J Gastroenterol 2007;13:37-8

How to cite this URL:
Azzam N. Angiogenesis and inflammatory bowel disease. Saudi J Gastroenterol [serial online] 2007 [cited 2022 Dec 9];13:37-8. Available from:

Angiogenesis is the process of new capillary formation from pre-existing vasculature in adult tissues.[1] It is a fundamental constituent of many complex biological processes. In the last three decades, angiogenesis has emerged as a phenomenon that is thought to be essential for the growth of tumors and non-neoplastic chronic inflammatory and autoimmune diseases as diverse as atherosclerosis, rheumatoid arthritis, diabetic retinopathy, psoriasis, and airway inflammation.[2],[3]

Growth of new blood vessels is intrinsic to inflammation leading to structural changes and capillary and venule remodeling, which in turn result in an expansion of the tissue micro vascular bed.[4],[5] The activated endothelium contributes to the local production of cytokines, chemokines, and matrix metalloproteinases.[6]

A prime example of the process of immune-driven angiogenesis is seen in rheumatoid arthritis in which neovascularization is one of the earliest histopathological findings and a key contributor to pannus formation. Similar phenomena are also observed in psoriasis.[7] Hence, it is expected that angiogenesis plays a role in the pathogenesis of Crohn's disease (CD) and ulcerative colitis (UC).[8] At present, only a handful of reports suggest the presence of an abnormal vascular bed in inflammatory bowel disease (IBD) tissue. One study employed immuno-histochemical staining of histologically normal controls and active CD and UC involved colonic tissue with antibodies specifically recognizing surface CD31 and intra-cytoplasmic von Willebrand/factor VIIIa, which are widely used endothelial markers.[9] Normal colon showed sporadic thin vessels in the lamina propria and submucosa, whereas tissue involved by CD or UC contained numerous readily detectable dilated vessels in both the lamina propria and submucosa. The microvascular density measured as total number of vessels per field, percentage section area, mean vessel area and mean larger vessel diameter, were all significantly increased in the lamina propria of CD and UC compared with histologically normal control specimens.[10]

   Vascular endothelial growth factors and angiogenesis in IBD Top

The microvascular changes associated with angiogenesis are key contributors to the tissue injury and remodeling process that inevitably accompanies chronic inflammation. A recent study found that increased vascularization is present in tissues involved by active inflammation, a finding compatible with the concept of immune-driven angiogenesis[11] and indicative of a direct codependency between angiogenesis and inflammation.

The activated lamina propria mononuclear cells (LPMCs) produce vascular endothelial growth factors (VEGF) and basic fibroblast growth factors (bFGF). Both angiogenetic factors enhance further inflammation. Previous studies showed that serum level of VEGF and bFGF was significantly higher in active IBD than those in controls.[12] A recent study assessed the levels of VEGF, IL-8 and bFGF, three major angiogenic factors, in mucosa extracted from control and IBD mucosa as measured by Western blot found all factors to be markedly increased in both CD and UC.[10] The cellular sources of these mediators were LPMCs. It was found that activated macrophages preferentially synthesize VEGF and bFGF, whereas both T-cells and macrophages are active producers of IL-8. In addition to immune cells, non-immune cells are also the rich source of angiogenic factors, particularly mesenchymal cells.[13] In another recent study it was shown that VEGF levels correlate well with disease activity and subsequently decrease with the use of different treatment modalities such as corticosteroids, thalidomide, and infliximab.[14]

   The future Top

Angiogenesis can be viewed as a double-edged weapon. On one side, it is beneficial in wound healing and repair, whereas on the other side, it promotes tissue damage in neoplastic and inflammatory disorders. In fact, promoting angiogenesis in animal models of rheumatoid arthritis, lung inflammation, psoriasis, and atherosclerosis causes worsening of disease.[15] This appears to be true also in experimental IBD models. Further supporting the role of angiogenesis in IBD pathogenesis is a preliminary report that VEGF polymorphisms are associated with susceptibility to human IBD.[16] Based on these observations, it seems logical that angiogenesis blockade could be beneficial in chronic inflammation, as documented in many other systems. Specific supporting evidence has been found using the IL-10-deficient model of colitis, where it was recently shown that there is a therapeutic effect of targeting angiogenesis by integrin -V-3 blockade.[17] In addition, some of the drugs effective in treatment of human IBD, such as infliximab and thalidomide, have potent antiangiogenic activity, implying conceptual bases for considering antiangiogenic strategies for IBD therapy as currently being tested in other autoimmune disorders.

   References Top

1.Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267:10931-4.  Back to cited text no. 1    
2.Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med 1971;285:1182-6.  Back to cited text no. 2  [PUBMED]  
3.Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27-31.  Back to cited text no. 3    
4.Majno G. Chronic inflammation: Links with angiogenesis and wound healing. Am J Pathol 1998;153:1035-9.  Back to cited text no. 4  [PUBMED]  [FULLTEXT]
5.Bagli E, Xagorari A, Papetropoulos A, Murphy C, Fotsis T. Angiogenesis in inflammation. Autoimmun Rev 2004;3:S26.  Back to cited text no. 5  [PUBMED]  
6.Szekanecz Z, Koch AE. Vascular endothelium and immune responses: Implications for inflammation and angiogenesis. Rheum Dis Clin North Am 2004;30:97-114.  Back to cited text no. 6  [PUBMED]  [FULLTEXT]
7.Creamer D, Sullivan D, Bicknell R, Barker J. Angiogenesis in psoriasis. Angiogenesis 2002;5:231-6.  Back to cited text no. 7  [PUBMED]  [FULLTEXT]
8.Fiocchi C. Inflammatory bowel disease: Etiology and pathogenesis. Gastroenterology 1998;115:182-205.  Back to cited text no. 8  [PUBMED]  [FULLTEXT]
9.Vermeulen PB, Gasparini G, Fox SB, Toi M, Martin L, McCulloch P, et al . Quantification of angiogenesis in solid human tumours: An international consensus on the methodology and criteria of evaluation. Eur J Cancer 1996;32A:2474-84.  Back to cited text no. 9    
10.Danese S, Sans M, de la Motte C, Graziani C, West G, Phillips MH, et al . Angiogenesis as a novel component of inflammatory bowel disease pathogenesis. Gastroenterology 2006;130:2060-73.  Back to cited text no. 10    
11.Romagnani P, Lasagni L, Annunziato F, Serio M, Romagnani S. CXC chemokines: The regulatory link between inflammation and angiogenesis. Trends Immunol 2004;25:201-9.  Back to cited text no. 11  [PUBMED]  [FULLTEXT]
12.Kanazawa S, Tsunoda T, Onuma E, Majima T, Kagiyama M, Kikuchi K. VEGF, basic FGF and TGF-beta in Crohn's and ulcerative colitis: A novel mechanism of chronic intestinal inflammation. Am J Gastroenterol 2001;96:822-8  Back to cited text no. 12  [PUBMED]  [FULLTEXT]
13.Kunz-Schughart LA, Knuechel R. Tumor-associated fibroblasts (part I): Active stromal participants in tumor development and progression? Histol Histopathol 2002;17:599-621.  Back to cited text no. 13    
14.Koutroubakis IE, Tsiolakidon G. Role of angiogenesis in inflammatory bowel disease Inflam Bowel Dis 2006;12:515-23.  Back to cited text no. 14    
15.Lee CG, Link H, Baluk P, Homer RJ, Chapoval S, Bhandari V, et al . Vascular endothelial growth factor (VEGF) induces remodeling and enhances TH2-mediated sensitization and inflammation in the lung. Nat Med 2004;10:1095-103.  Back to cited text no. 15    
16.Ferrante M, Henckaerts L, Hlavaty T, Pierik M, Bueno de Mesquita M, et al . Vascular endothelial growth factor (VEGF) polymorphisms are implicated in susceptibility to IBD. Gastroenterology 2005;128:A441.  Back to cited text no. 16    
17.Danese S, Sans M, Spencer DM, Beck I, Fernando D, Plunkett M, et al . Starving the inflamed gut: Angiogenesis blockade as a novel therapeutic approach to experimental colitis. Gastroenterology 2005;128:A40.  Back to cited text no. 17    

Correspondence Address:
Nahla Azzam
Division of Gastroenterology, King Khalid, P. O. Box 2925 (59), Riyadh 11461
Saudi Arabia
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Source of Support: None, Conflict of Interest: None

DOI: 10.4103/1319-3767.30464

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