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P051. Angiogenic and lymphangiogenic protein level alterations in colonic mucosa culture supernatant and peripheral blood in patients with inflammatory bowel disease (IBD)

A. Algaba1, P.M. Linares2, M.E. Fernández-Contreras2, J. Trápaga1, A. Ordoñez1, I. Guerra1, M. Chaparro2, J.L. Rodríguez-Agulló1, J.P. Gisbert2, F. Bermejo1

1Fuenlabrada University Hospital, Fuenlabrada, Spain; 2La Princesa University Hospital, Madrid, Spain

Aim: To study the main angiogenic and lymphangiogenic factors (ALF) and their receptors in both colonic mucosa culture supernatant and peripheral blood of patients with IBD.

Methods: Descriptive, transversal study in 21 non-IBD controls (CTR) and 60 patients with active or quiescent IBD based on endoscopic criteria. From each patient, a peripheral blood sample was taken and centrifuged for obtaining serum. Several intestinal mucosa samples were taken during the colonoscopy and cultured for 24 h. Concentrations of VEGFA, VEGFC, VEGFD, VEGFR1, VEGFR2, VEGFR3, PlGF, Ang1, Ang2 and Tie2 in serum and tissue culture supernatant were determined by ELISA assay.

Results: 15 patients were included in each group based on the following endoscopic classification: active ulcerative colitis (AUC), quiescent ulcerative colitis (QUC), colonic active Crohn's disease (ACD) and quiescent Crohn's disease (QCD). A positive correlation between serum and colonic mucosa culture supernatant levels of VEGFC (p = 0.04), VEGFD (p = 0.007), VEGFR1 (p = 0.017), Ang1 (p = 0.002) and Tie-2 (p = 0.006) was found.

  VEGFPlGFVEGFCVEGFDVEGFR1VEGFR2VEGFR3Ang1Ang2Tie2
CTRS445
±290
35
±5
10
±2
702
±384
158
±43
12
±2
3
±1.4
39
±13
1464
±471
25
±4
 T11
±5
1.3
±0.7
9
±3
4
±1.3
11
±9
2
±1.7
69
±45
72
±4
22
±6
7
±2.6
AUCS557
±265a
32
±6
12
±3
824
±661.3
184
±35
11
±2
5
±2.2*
58
±9*
1457
±575
32
±7*
 T21
±9*a
3
±1.2*a
15
±9
8
±2.6*a
22
±16*a
4
±4
75
±24
14
±6*a
40
±18*a
16
±10*a
QUCS338
±230
34
±8
11
±2
599
±240
164
±51
12
±3
4
±2
50
±13*
1502
±382
29
±6*
 T12
±6
1.4
±0.9
8
±3
5
±2
4
±8
1.8
±1.8
66
±39
8
±3
21
±9
8
±3
ACDS584
±502
35
±4
13
±5
754
±413
146
±30
10
±2
3
±0.9
61
±23*a
1693
±967
29
±5*
 T20
±11*a
3
±1.8*a
11
±3a
6
±3*a
15
±11
2
±1.5
86
±88
11
±4*a
35
±14*a
15
±6*a
QCDS388
±244
31
±6
10
±3
640
±388
150
±46
12
±2.9
4
±1.6
46
±15
1559
±493
30
±6*
 T10
±4
1.3
±0.7
7
±4
4
±1.7
9
±5
1.6
±1.3
51
±32
7
±3
20
±8
8
±3
S: Serum concentration. VEGFA, PlGF, VEGFC, VEGFR1 and Ang2 concentrations are expressed in pg/ml, all other proteins in ng/ml. T: tissue supernatant concentration in pg/ml per mg of tissue. *Significant differences compared to non-IBD controls (p < 0.05). aSignificant differences compared to patients in remission (p < 0.05).

Conclusions:

  1. The levels of the main angiogenic and lymphangiogenic factors in colonic mucosa culture supernatant are significantly higher in patients with active IBD than in non-IBD controls.
  2. When IBD patients achieve endoscopic remission, concentration of the main angiogenic and lymphangiogenic factors in colonic mucosa culture supernatant decrease, reaching similar values to the controls.
  3. Patients with active or quiescent IBD have significant higher serum levels of Tie-2 than controls.
  4. A significant correlation was found between serum and colonic mucosa culture supernatant levels for VEGFC, VEGFD, VEGFR, Ang1 and Tie2.