|
|
| Year : 2007 | Volume
: 13
| Issue : 1 | Page : 37-38 |
|
| Angiogenesis and inflammatory bowel disease |
|
|
Nahla Azzam
Division of Gastroenterology, King Khalid University Hospital, Riyadh, Saudi Arabia
Click here for correspondence address and email
| Date of Submission | 19-Oct-2006 |
| Date of Acceptance | 23-Dec-2006 |
|
|
 |
|
 Abstract | | |
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 |
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 | |  |
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 | | |
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 | | |
| 1. | Folkman J, Shing Y. Angiogenesis. J Biol Chem 1992;267:10931-4.  |
| 2. | Folkman J. Tumor angiogenesis: Therapeutic implications. N Engl J Med 1971;285:1182-6. [PUBMED] |
| 3. | Folkman J. Angiogenesis in cancer, vascular, rheumatoid and other disease. Nat Med 1995;1:27-31. |
| 4. | Majno G. Chronic inflammation: Links with angiogenesis and wound healing. Am J Pathol 1998;153:1035-9. [PUBMED] [FULLTEXT] |
| 5. | Bagli E, Xagorari A, Papetropoulos A, Murphy C, Fotsis T. Angiogenesis in inflammation. Autoimmun Rev 2004;3:S26. [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. [PUBMED] [FULLTEXT] |
| 7. | Creamer D, Sullivan D, Bicknell R, Barker J. Angiogenesis in psoriasis. Angiogenesis 2002;5:231-6. [PUBMED] [FULLTEXT] |
| 8. | Fiocchi C. Inflammatory bowel disease: Etiology and pathogenesis. Gastroenterology 1998;115:182-205. [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. |
| 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. |
| 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. [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 [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. |
| 14. | Koutroubakis IE, Tsiolakidon G. Role of angiogenesis in inflammatory bowel disease Inflam Bowel Dis 2006;12:515-23. |
| 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. |
| 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. |
| 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. |
Correspondence Address:
Nahla Azzam
Division of Gastroenterology, King Khalid, P. O. Box 2925 (59), Riyadh 11461
Saudi Arabia
 Source of Support: None, Conflict of Interest: None  | Check |
DOI: 10.4103/1319-3767.30464
|
|
| This article has been cited by | | 1 |
A heteropolysaccharide, l-fuco-d-manno-1,6-a-d-galactan extracted from Grifola frondosa and antiangiogenic activity of its sulfated derivative |
|
| Ying Wang,Xiaokun Shen,Wenfeng Liao,Jianping Fang,Xia Chen,Qun Dong,Kan Ding | | Carbohydrate Polymers. 2014; 101: 631 | | [Pubmed] | [DOI] | | | 2 |
Role of growth factors in the development of lymphangiogenesis driven by inflammatory bowel disease: A review |
|
| Pablo M. Linares, Javier P. Gisbert | | Inflammatory Bowel Diseases. 2010; : n/a | | [VIEW] | [DOI] | |
|
|
|
|
|
|
|
|
|
|
|
|
| Article Access Statistics | | | Viewed | 3791 | | | Printed | 197 | | | Emailed | 2 | | | PDF Downloaded | 590 | | | Comments | [Add] | | | Cited by others | 2 | | |
|
|
