Serum Calprotectin as a Novel Biomarker in Abdominal Aortic Aneurysm Pathogenesis and Progression: Preliminary Data from Experimental Model in Rats.
Abdominal aortic aneurysm (AAA) formation is associated with by inflammation and matrix degradation. This study tested the hypothesis that calprotectin, a novel biomarker for inflammation, as well as established biomarkers such as C-reactive protein (CRP) and matrix metalloproteinase- 9 (MMP-9) could also be indicative inflammatory biomarkers during AAA pathogenesis and progression. We also evaluated the correlation of serum soluble Receptor for Advanced Glycation End Products (sRAGE) with AAA diameter and serum calprotectin levels.



Rat abdominal aortas were perfused with porcine pancreatic elastase (AAA Group) or saline (Control Group) and studied on post-perfusion days 7 and 14 (n=11 per treatment group). Aneurysm was defined as a dilatation of the aorta above 150% of its original diameter. Laparotomy was performed on days 0 (T0), 7 (T7) and 14 (T14) for aortic diameter measurement. At the same time intervals, we measured the serum levels of calprotectin, CRP, sRAGE and MMP-9.



All animals developed AAA and no rupture occurred. MMP-9 in AAA group at T14 (p<0.05 compared with T7 and p<0.005 compared with T0) and calprotectin in AAA group at T14 (p<0.001 compared with T7 and T0) continued to significantly increase at all times. Serum sRAGE was significantly lower in the AAA group compared with the control group and within AAA group at all time points (p<0.001). On the other hand, the highest levels of CRP were identified at T7 in both groups. Calprotectin concentrations in AAA group were significantly higher compared with controls at T7 and T14 (p<0.001 and p<0.001, respectively). Aortic diameter was significantly correlated with MMP-9 and calprotectin serum concentrations at all time points (r=0.51, p<0.001; r=0.728, p<0.001 respectively). Serum sRAGE levels were significantly correlated with aortic diameter at all time points (r=-0.48, p<0.001) and serum calprotectin levels (r=-0.22, p<0.001).



This is the first evaluation of calprotectin as an AAA inflammation biomarker. It seems to be a promising marker related to AAA natural history. Further experimental and large human studies are needed to fully elucidate the role of calprotectin in the development and progression of AAAs.
1st Department of Surgery, "Laikon" General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.|Department of Immunology, Lerner Research Institute, Cleveland Clinic, Cleveland, Ohio, USA.
Demetrios
D
Moris
Department of Pathology, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Stamatios
S
Theocharis
1st Department of Surgery, "Laikon" General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Spyridon
S
Davakis
1st Department of Surgery, "Laikon" General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Nikolaos
N
Patelis
Department of Pathology, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Georgios
G
Agrogiannis
Laboratory for Experimental Surgery and Surgical Research "N.S. Christeas", Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Ioannis S
IS
Vlachos
Laboratory for Experimental Surgery and Surgical Research "N.S. Christeas", Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Eleftherios
E
Spartalis
1st Department of Surgery, "Laikon" General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Antonios
A
Athanasiou
1st Department of Surgery, "Laikon" General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Chris
C
Bakoyiannis
Laboratory for Experimental Surgery and Surgical Research "N.S. Christeas", Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Despina N
DN
Perrea
1st Department of Surgery, "Laikon" General Hospital, Medical School of Athens, National and Kapodistrian University of Athens, Athens, Greece.
Sotirios
S
Georgopoulos
D000818:Animals; D001012:Aorta, Abdominal / Q000378:metabolism* / Q000473:pathology; D017544:Aortic Aneurysm, Abdominal / Q000097:blood* / Q000139:chemically induced / Q000473:pathology; D015415:Biomarkers / Q000097:blood; D002097:C-Reactive Protein / Q000378:metabolism; D004108:Dilatation, Pathologic; D004195:Disease Models, Animal; D006801:Humans; D018836:Inflammation Mediators / Q000097:blood*; D039841:Leukocyte L1 Antigen Complex / Q000097:blood*; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D010196:Pancreatic Elastase; D000074286:Preliminary Data; D017208:Rats, Wistar; D000067759:Receptor for Advanced Glycation End Products / Q000097:blood
C000593874:Ager protein, rat; D015415:Biomarkers; D018836:Inflammation Mediators; D039841:Leukocyte L1 Antigen Complex; D000067759:Receptor for Advanced Glycation End Products; D002097:C-Reactive Protein; D010196:Pancreatic Elastase; D020780:Matrix Metalloproteinase 9; C572337:Mmp9 protein, rat
AAA; Abdominal aortic aneurysms; biomarkers; calprotectin; inflammation; progression