IBD (Crohn's, Colitis) 'joins' cancer, inflammatory diseases in associated blood vessel growth

September 13, 2004

Snowmass, Co. (September 13, 2004) -- Over at least the last decade it has been recognized that the growth of new blood vessels is critical in the pathogenesis of cancer because it increases blood supply to malignant tissue. Relatively recently, a novel pathogenic role of angiogenesis has been established for such chronic inflammatory diseases as rheumatoid arthritis, psoriasis and atherosclerosis.

As a result, suppressing neoangiogenesis is being investigated as a therapeutic approach for not only cancer, but also chronic inflammation.

Whether neoangiogenesis also occurs in Crohn's Disease (CD) and ulcerative colitis (UC), the major constituents of Inflammatory Bowel Diseases (IBD), has never been studied, according to the authors of a paper presented at an IBD translational conference sponsored by the American Physiological Society.

The paper is entitled, "Neoangiogenesis: a new component in Inflammatory Bowel Diseases pathogenesis."

Lead author Silvio Danese of Case Western Reserve University School of Medicine and Universita' Cattolica del S. Cuore, Rome, Italy, collaborated with colleagues Miquel Sans, Brenda Reyes-Rivera, Gail West, Homa Phillips, Joe Willis and Claudio Fiocchi at Case Western Reserve University School of Medicine; Carol de la Motte at the Cleveland Clinic Foundation; and Roberto Pola and Antonio Gasbarrini at Universita' Cattolica del S. Cuore.

According to Danese, "Our results show that increased vascularization is present in IBD, and the inflamed mucosal microenvironment actively promotes angiogenesis." Furthermore, he said that "the intestinal microvascularization of both CD and UC displays an activated profile as shown by the expression of angiogenic marker áVâ3 integrin.

"Targeting this integrin could be a potential therapeutic approach for IBD," similar to approaches in other forms of chronic inflammation, Danese said. "These results provide the initial material and conceptual framework for investigating angiogenesis in IBD both as a pathogenic component as well as a possible therapeutic target," he added.

Methodology and results

The researchers took normal control and actively involved IBD colonic mucosa and immunostained them for the endothelial antigen CD31. Vessels were quantified by digital morphometry (vessel density/field). Microvessel áVâ3 expression was studied in vivo by confocal microscopy, and in vitro by flow cytometric analysis of human intestinal microvascular endothelial cells (HIMEC) activated by bFGF, VEGF and TNF-á. Pro-angiogenic bioactivity of mucosal extracts was tested in vitro by induction of HIMEC migration (cells/field) and in vivo by the mouse corneal angiogenesis assay.

They found that microvessel density was significantly higher in CD and UC compared with control mucosa. áVâ3 expression was only sporadically detected in normal mucosa, whereas it was ubiquitously and strongly expressed in IBD microvasculature as confirmed by co-localization with CD31. The expression of áVâ3 by HIMEC was upregulated by bFGF and TNF-á but not VEGF, and its targeting with a specific antibody (Vitaxin) induced marked HIMEC apoptosis. HIMEC migration was dose-dependently induced by both CD and UC mucosal extracts, and was significantly greater than that induced by control extracts, the researchers reported. As shown by neutralizing antibodies, migration was primarily dependent on IL-8, and less on bFGF or VEGF. Finally, IBD-derived extracts induced a potent angiogenic response in the corneal assay compared to control-derived extracts, they noted.

Conclusion

The results provide "morphological and functional evidence of strong pro-angiogenic activity in both CD and UC mucosa, indicating that the local microvasculature undergoes an intense process of neoangiogenesis in IBD," the paper said. The authors said this "suggests that neoangiogenesis is a vital component of IBD pathogenesis, and provides the material and conceptual framework for considering anti-angiogenic therapies for IBD as is currently ongoing in other autoimmune disorders."
-end-
The APS conference, "Immunological and Pathophysiological Mechanisms in Inflammatory Bowel Diseases" was also supported by Centocor Inc., Hoffman-La Roche Inc., the National Institutes of Health-NIDDK, and the Crohn's and Colitis Foundation of America.

For a complete list of the speakers and topics at the conference please go to: http://www.the-aps.org/press/conference/ibd04conf.htm

Other press releases from the conference can be found at: http://www.the-aps.org/press/conference/

Editor's note: Telephone or in-person media interviews can be arranged with any of the speakers by contacting Mayer Resnick at APS headquarters -- 301-634-7209 (office), 301-332-4402 (cell) or mresnick@the-aps.org.

Next meeting


APS Intersociety Meeting on the INTEGRATIVE BIOLOGY OF EXERCISE

Co-sponsored by the American Physiological Society, Canadian Society for Exercise Physiology and the American College of Sports Medicine
Oct. 6-9, 2004, Austin, Texas
http://www.the-aps.org/meetings/aps/austin/index.htm


The American Physiological Society was founded in 1887 to foster basic and applied bioscience. The Bethesda, Maryland-based society has more than 10,000 members and publishes 14 peer-reviewed journals containing almost 4,000 articles annually.

APS provides a wide range of research, educational and career support and programming to further the contributions of physiology to understanding the mechanisms of diseased and healthy states. In May, APS received the Presidential Award for Excellence in Science, Mathematics and Engineering Mentoring (PAESMEM).


American Physiological Society

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