E010 Increase in circulating microparticles in inflammatory bowel disease patients induces vascular alterations

Abstract

Among the proposed hypothesis for inflammatory bowel disease (IBD) pathogenesis, a vascular cause has been suggested, mostly in reference to anatomic and pathological studies. We previously reported in small mesenteric arteries from Crohn's disease patients a balance between vasoconstrictor products from cyclooxygenase and unidentified vasodilatory products that maintained vascular reactivity in a physiological range despite an increase of circulatory cytokines in these patients (Tabernero et al., Circulation, 2003). Microparticles (MPs) are membrane vesicles released during cell activation and apoptosis. Elevated levels of circulating MPs have been detected in pathologic conditions and their increase has been associated with disease activity and/or prognosis. We investigated whether MPs from IBD patients may play a role in the regulation of endothelial function and vascular reactivity in this disease. Blood samples were obtained either from IBD patients as well as age and sex-matched healthy subjects. MPs concentration and origin were assessed by flow cytometry using specific antibodies. Male Swiss mice were injected intravenously with MPs from IBD patients or with saline solution and sacrified after 24 hours. Endothelial function and vascular reactivity were studied on aortic rings and small mesenteric resistance arteries (SMA) by myography and arteriography, respectively. Patients with IBD displayed increased circulating levels of MPs compared to healthy subjects including those from procoagulant, platelet and activated platelet, endothelial, leukocyte and erythrocyte origins. In aorta, MPs from IBD patients compared to saline significantly reduced both endothelium-dependent relaxation to acetylcholine and contraction to serotonin. In SMA, although MPs from IBD patients did not affect flow-induced dilation, a reduced NO-component that was completely compensated by the endothelium-derived hyperpolarizing factor-component of the response was highlighted. Besides, MPs from IBD did not affect myogenic tone in SMA. These results provide further evidence of increased circulating levels of MPs in patients with IBD. MPs origin may play a role in enhanced coagulation and inflammatory states reported in IBD patients. Finally, MPs from IBD patients influence both endothelial dysfunction and vascular hyporeactivity in the experimental model used. (Partially supported by Ferring France Laboratories).