Angiopoietin-2, a regulator of vascular permeability in inflammation, is associated with persistent organ failure in patients with acute pancreatitis from the United States and Germany.
OBJECTIVE
Patients with severe acute pancreatitis (AP) typically develop vascular leak syndrome, resulting in hemoconcentration, hypotension, pulmonary edema, and renal insufficiency. Angiopoietin-1 (Ang-1) and 2 (Ang-2) are autocrine peptides that reduce or increase endothelial permeability, respectively. The aim of this study was to determine whether Ang-1 and/or Ang-2 levels are predictive biomarkers of persistent organ failure (>48 h) and prolonged hospital course.


METHODS
Banked serum from 28 patients enrolled in the Severity of Acute Pancreatitis Study at the University of Pittsburgh Medical Center (UPMC) and 58 controls was analyzed for Ang-1 and Ang-2 levels. Separately, serum from 123 patients and 103 controls at Greifswald University (GU), Germany was analyzed for Ang-2 levels. Angiopoietin levels were measured by enzyme-linked immunosorbent assay.


RESULTS
In all, 6 out of 28 UPMC patients (21%) and 14 out of 123 GU patients (13%) developed persistent organ failure and were classified as severe AP. Ang-2 was significantly higher on admission in patients who developed persistent organ failure compared with those who did not in UPMC (3,698 pg/ml vs. 1,001 pg/ml; P=0.001) and GU (4,945 pg/ml vs. 2,631 pg/ml; P=0.0004) cohorts. After data scaling, admission Ang-2 levels showed a receiver-operator curve of 0.81, sensitivity 90%, and specificity 67% in predicting persistent organ failure. In addition, Ang-2 levels remained significantly higher in severe AP compared with mild AP patients until day 7 (days 2-4: P<0.005; day 7: P<0.02). Ang-1 levels were not significantly different between mild and severe AP patients on admission.


CONCLUSIONS
Elevated serum Ang-2 levels on admission are associated with and may be a useful biomarker of predicting persistent organ failure and ongoing endothelial cell activation in AP.
Whitcomb
David C
DC
Department of Medicine, University of Pittsburgh Medical Center, Pennsylvania, USA. whitcomb@pitt.edu
Muddana
Venkata
V
Langmead
Christopher J
CJ
Houghton
Frank D
FD
Guenther
Annett
A
Eagon
Patricia K
PK
Mayerle
Julia
J
Aghdassi
Ali A
AA
Weiss
F Ulrich
FU
Evans
Anna
A
Lamb
Janette
J
Clermont
Gilles
G
Lerch
Markus M
MM
Papachristou
Georgios I
GI
D000368:Aged; D042683:Angiopoietin-1 / Q000097:blood; D042702:Angiopoietin-2 / Q000097:blood*; D015415:Biomarkers / Q000097:blood; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D005858:Germany; D006801:Humans; D008297:Male; D008875:Middle Aged; D009102:Multiple Organ Failure / Q000097:blood*; D019283:Pancreatitis, Acute Necrotizing / Q000097:blood*; D011237:Predictive Value of Tests; D012372:ROC Curve; D012720:Severity of Illness Index; D014481:United States
D042683:Angiopoietin-1; D042702:Angiopoietin-2; D015415:Biomarkers