Soluble Selectins, sICAM, sVCAM, and Angiogenic Proteins in Different Activity Groups of Patients with Inflammatory Bowel Disease

Abstract

The endothelium is involved in the pathogenesis of inflammatory bowel disease (IBD). So far knowledge of the precise role of soluble adhesion molecules and angiogenic factors at different periods of activity in IBD is scarce or contradictory. Our goal in this study was to determine the serum levels of adhesion molecules and angiogenic factors in IBD patients at different periods of disease activity--clinical remission, biochemical evidence of inflammation, and clinical evidence of activity. We used a cross-sectional study design consisting of 218 patients (145 with Crohn's disease [CD] and 73 with ulcerative colitis [UC]) and 115 randomly assymptomatic blood donors. To assess disease activity, Harvey and Bradshaw's and Truelove-Witts' indexes were used. Circulating plasma sE-selectin (sE-S), sP-selectin (sP-S), human soluble vascular cell adhesion molecule-1 (sVCAM-1), and human soluble intercellular adhesion molecule-1 (sICAM-1) and serum levels of human vascular endothelial growth factor (VEGF), angiogenin (ANG), and placenta growth factor (P/GF) were measured with ELISAs. The amount of mRNA VEGF in blood mononuclear cells was also evaluated. In inactive CD patients, serum levels of sP-S, sE-S, sVCAM, and sICAM were significantly lower (P < 0.05) than in controls. In active CD patients, only the sE-S values were higher than in controls. In UC patients, sP-S and sVCAM levels were significantly lower than those in controls. Considering growth factors, CD patients in remission had levels of ANG and VEGF lower than those found in controls. The VEGF RNAm in blood mononuclear cells was similar among all CD activity groups. In conclusion, in UC patients the serum levels of VEGF, ANG, and P/GF were similar to those in controls. The serum levels of adhesion molecules and angiogenic factors were low in IBD patients in periods of remission. Low levels of angiogenic factors in inactive CD patients suggest dysfunction of the angiogenic process and wound repair.

Corticosteroids Modulate Angiogenic Soluble Factors in Ulcerative Colitis Patients

“…In previous studies, an increased expression of VEGF protein and VEGF mRNA in UC patients had already been observed in comparison with those found in healthy controls [25,[34][35][36][37][38]. Our results were consistent with those found in previous studies using active UC patient blood samples [25,34,35].…”

Molecular Imaging of Inflammation in Inflammatory Bowel Disease with a Clinically Translatable Dual-Selectin–targeted US Contrast Agent: Comparison with FDG PET/CT in a Mouse Model

“…Vascular endothelial cell expression of E-selectin is entirely under transcriptional control, and cell surface expression can be detected approximately 2 hours after acute stimulation (29,31,32). In patients with IBD, both P-selectin and E-selectin have been shown to be constitutively expressed on inflamed vascular endothelium during the active phase of the disease (7,(33)(34)(35). Thus, both markers could be further evaluated as promising imaging biomarkers with In murine colitis models, it has been shown that FDG uptake was specifically correlated with glucose transporter 1 expression by CD4 + T cells, and those cells were identified as the major cellular source of FDG uptake in murine colitis (20).…”

Multipotent role of platelets in inflammatory bowel diseases: A clinical approach

“…P selectin is a member of the CAMs family mainly produced in PLT. A soluble fraction of P-selectin is also detected in patients with inflammatory disorders, including IBD, and possibly serves as selectin binding inhibitor [63] . The lectin containing N-terminal domain of P-selectin binds to P-selectin glycoprotein ligand (PSGL-1) found in leukocytes (mainly polymorphonuclears) mediating recruitment and rolling of infiltrating leukocytes in the gut mucosa, and initiating activation processes like chemokines production by monocytes and CD4(+) T-cells, as well as superoxide overexcretion by neutrophils [1] .…”