P058. In vivo formation of 8-iso-prostaglandin F2 α and platelet activation in inflammatory bowel disease
A. Di Sabatino1, P. Biancheri1, P. Giuffrida1, M. Guerci1, C. Salvatore1, A. Massari1, N. Vazzana2, S. Sestili2, S. Lattanzio2, R. Liani2, G. Davì2, G.R. Corazza1, 1IRCCS Policlinico San Matteo, Pavia, Italy, 2Internal Medicine and Center of Excellence on Aging, Chieti-Pescara, Italy
Patients with inflammatory bowel disease (IBD), namely Crohn's disease (CD) and ulcerative colitis (UC), have a higher risk of cardiovascular disease (CVD) despite having a lower burden of traditional risk factors. We previously reported that several inflammatory diseases are associated with enhanced lipid peroxidation and persistent platelet activation. Platelets from patients with CD release more soluble CD40L than control subjects and this might be responsible, at least in part, for the platelet hyperactivation observed in CD. Thus, we aimed at characterizing the determinants of thromboxane (TX)-dependent platelet activation in this setting, with particular reference to enhanced lipid peroxidation and the CD40-CD40L system.
Blood and urinary samples were taken from 50 patients with IBD (27 with CD and 23 with UC, mean age 44±16 years, 14 males) and 30 age- and gender-matched healthy subjects. Among CD patients, 12 (44.4%) had ileo-colonic or colonic disease, whereas 15 (55.6%) had ileal disease. Among UC patients, 5 (21.7%) had a left-sided colitis and 17 (73.9%) had a pancolitis. Patients were being treated with salicylates (54.0%), azathioprine (10%), methotrexate (4.0%), corticosteroids (4.0%) or anti-TNF agents (34.0%). Plasma sCD40L and urinary levels of 8-iso-PGF2 α and 11-dehydro-TXB2 were measured in IBD patients and control subjects and a cross-sectional comparison was performed.
IBD patients had significantly higher urinary 8-iso-PGF2 α and 11-dehydro-TXB2 than control subjects (P < 0.0001). Circulating levels of sCD40L were also significantly higher in IBD patients as compared to healthy controls (P < 0.0001). In both IBD patients and control subjects, a significant direct correlation was found between urinary 8-iso-PGF2 α and 11-dehydro-TXB2 (Rho = 0.68, p < 0.0001).
This study provides biochemical evidence of enhanced TX-dependent platelet activation associated with oxidative stress in patients with IBD. Platelet-derived inflammatory molecules, such as sCD40L, may also play a critical role in both intestinal disease and atherothrombosis. Further studies are underway in order to establish whether platelet-derived biomarkers correlate with the incidence of CVD in IBD. Our results may also provide the rationale for targeting platelet activation to improve both IBD activity and cardiovascular risk in this setting.