HomeENGLISH MAGAZINECrohn disease: to overcome inflammation, you have to take the "right vessel"

Crohn disease: to overcome inflammation, you have to take the “right vessel”

In Germany alone there are around 400,000 patients who suffer from chronic inflammatory bowel diseases, like Crohn disease. For the first time, researchers at Universitätsklinikum Erlangen have discovered that dysfunctions in blood vessels play a significant role in the development of such diseases. Diseases in humans are often caused by malfunctioning cells. Epithelium cells, which form the barrier between the bowel and surrounding tissue, and inflammatory cells have been the focus of investigations of the mechanisms of chronic inflammatory diseases of the bowel up to now. Only recently, it has been recognized that the intestinal vascular endothelium represents a second important barrier in the gut. Situated between the bloodstream and the epithelial barrier, the intestinal vascular endothelium regulates blood supply, nutrient transport, tissue fluid homeostasis, and immune cell transmigration, while being nonpermissive to bacterial penetration. During IBD, inflammation has been shown to activate angiogenesis. In accord with this, increased levels of angiogenic growth factors like vascular endothelial growth factor A (VEGF-A), placental growth factor (PGF), and platelet-derived growth factor (PDGF), have been detected in the inflamed mucosa and the blood of patients with active disease.

In experimental model systems, the progression of the disease slowed down significantly by eliminating these dysfunctions. The researchers have now published their results in the Journal of Clinical Investigation. In conjunction with groups at the Department of Medicine 1- Gastroenterology, Pneumology and Endocrinology at Universitätsklinikum Erlangen and the Optical Imaging Centre Erlangen (OICE) at FAU, a group of researchers in molecular and experimental surgery at the Department of Surgery has now conducted an in-depth investigation of the role of blood vessels. The interdisciplinary cooperation project, which was primarily implemented by Victoria Langer as part of her doctoral thesis, discovered that the blood vessels of patients with chronic inflammatory bowel disease are especially permeable. In molecular analyses, the researchers identified the cause as a malfunction in the cell to cell interaction in endothelial cells. The dysfunction is caused by a specific cytokine known as interferon-γ, which is present in higher concentrations in chronically inflamed intestinal tissue. The increased permeability of blood vessels was proven in various experimental models and in patients with chronic inflammatory bowel diseases.

The significance of blood vessel permeability was demonstrated using genetic methods in experiments in animal models as the ability of endothelial cells to react to interferon-γ was inhibited, which significantly slowed down the progression of the disease. A significant clinical finding is that the drug Imatinib (Gliveec®), also inhibits vessel permeability, which also significantly suppressed disease progression. Imatinib is currently mainly used to treat cancer, especially leukemias AND lung cancer. Recently it has been shown that IFN-γ can induce members of the Abelson (Abl) family of nonreceptor tyrosine kinases in certain cell types. Notably, Abl kinases are required for VEGF- and thrombin-induced disruption of adherens junctions, and imatinib is a potent inhibitor of Abl kinase activity. The clinical responses of UC/CD patients under imatinib treatment might be due to the restoration of the endothelial barrier, which opens attractive future perspectives. Fontolizumab, an IFN-γ inhibitor, has yielded only limited therapeutic responses in IBD patients. However, fontolizumab therapy was not controlled for its impact on vascular permeability, which might improve the identification of effective treatment doses and patients responding to this therapy.

The study conducted by the researchers in Erlangen proves for the first time the great significance of the cardiovascular system in chronic inflammatory bowel diseases and opens up new approaches for treatments.

  • Edited by Dr. Gianfrancesco Cormaci, PhD, specialist in Clinical Biochemistry.

Scientific references

Langer V, Vivi E et al., Stürzl M. J Clin Invest. 2019 Sep 30.

Nardone OM et al. Therap Adv Gastroenterol. 2019 Jul 18.

Bernardino VR et al. Eur J Intern Med. 2019 Apr; 62:e16.

Dott. Gianfrancesco Cormaci
- Laurea in Medicina e Chirurgia nel 1998 (MD Degree in 1998) - Specialista in Biochimica Clinica nel 2002 (Clinical Biochemistry residency in 2002) - Dottorato in Neurobiologia nel 2006 (Neurobiology PhD in 2006) - Ha soggiornato negli Stati Uniti, Baltimora (MD) come ricercatore alle dipendenze del National Institute on Drug Abuse (NIDA/NIH) e poi alla Johns Hopkins University, dal 2004 al 2008. - Dal 2009 si occupa di Medicina personalizzata. - Guardia medica presso strutture private dal 2010 - Detentore di due brevetti sulla preparazione di prodotti gluten-free a partire da regolare farina di frumento immunologicamente neutralizzata (owner of patents concerning the production of bakery gluten-free products, starting from regular wheat flour). - Responsabile del reparto Ricerca e Sviluppo per la società CoFood s.r.l. (leader of the R&D for the partnership CoFood s.r.l.) - Autore di un libro riguardante la salute e l'alimentazione, con approfondimenti su come questa condizioni tutti i sistemi corporei. - Autore di articoli su informazione medica e salute sui siti web salutesicilia.com, medicomunicare.it e in lingua inglese sul sito www.medicomunicare.com
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