P067 Angiogenic characterisation of Crohn’s disease mesenteric adipose tissue
M. Eddama*1, R. Cohen1, M. Rodriguez-Justo2, I. Evans3, L. Shen4, L. Clapp4, M. Loizidou5
1University College London Hospital, Colorectal Surgery, London, United Kingdom, 2University College London Hospital, Department of Pathology, London, United Kingdom, 3University College London, Centre for Cardiovascular Biology and Medicine, London, United Kingdom, 4University College London, Institute of Cardiovascular Science, London, United Kingdom, 5University College London, Academic Department of Surgery, London, United Kingdom
Mesenteric fat wrapping is a prominent pathological feature of Crohn’s disease (CD). The role of the mesentery in CD is poorly understood. We hypothesise that mesenteric adipose tissue (AT) has dysregulated angiogenesis that may play a role in the inflammatory response in CD.
Fresh tissue samples from bowel (terminal ileum), as well as mesenteric, omental, and subcutaneous AT, were collected from 17 CD and 9 control patients who underwent ileocolonic resection. Angiogenic gene expression was investigated by RT-polymerase chain reaction (PCR) gene array of 84 genes involved in human angiogenesis. This was conducted to compare 12 CD mesenteric AT and 8 controls. Subsequently, the levels for 24 selected angiogenic genes were assessed by RT PCR on 48 AT samples and 16 bowel samples. Further, the levels for interleukin (IL) 6 and vascular endothelial growth factor A (VEGFA) protein expression were measured using ELISA.
All the patients in the disease group had an established pathological diagnosis of CD with mesenteric fat wrapping. There was down regulation of pro and anti-angiogenic gene expression in the CD mesenteric AT in comparison with control. Specifically, IL 6 and VEGFA were significantly (p < 0.001) down regulated by 8 and 2.3 fold, respectively. In CD mesenteric AT the down regulation of IL6 was significantly (p < 0.0001), positively correlated (r = 0.93, 95% CI 0.76, 0.98) with VEGFA. A similar gene expression pattern was seen in the bowel tissue; however, the difference did not reach statistical significance. Protein expression also demonstrated a significantly (p < 0.01) lower level of IL6 and VEGFA in the mesenteric AT of CD patients in comparison to control. A similar pattern of IL6 and VEGFA protein expression was seen in the bowel tissue; however, again, this was not statistically significant.
The mesenteric fat wrapping tissue of well-established CD demonstrate dysregulated angiogenesis as well as immunodeficiency. Therefore, at this stage of the disease, further investigations may be required to establish the implications of anti-angiogenic and immunosuppressive therapy.