Plasma levels of matrix metalloproteinase-9: a possible diagnostic marker of successful endovascular aneurysm repair.

OBJECTIVE: The aim of the study was evaluating the diagnostic value of plasma matrix metalloproteinase- (MMP)-2 and -9 and tissue inhibitor of MMP-1 (TIMP-1) for endoleak detection after endovascular aneurysm repair (EVAR). REPORT: Consecutive EVAR patients (n = 17) with endoleak and matched controls without endoleak (n = 20) were prospectively enrolled. Increased levels of MMP-9 were observed in patients with endoleak (P < 0.001). Regression analysis showed no significant influence of age, sex or abdominal aortic aneurysm (AAA) size. The receiver operating characteristic (ROC) curve of plasma MMP-9 levels showed that a cut-off value of 55.18 ng ml(-1) resulted in 100% sensitivity and 96% specificity with an AUC value of 0.988 (P < 0.001) to detect endoleak. CONCLUSIONS: Plasma MMP-9 levels appear to discriminate between patients with and without an endoleak with high sensitivity and specificity.

Differential protein expression in serum of abdominal aortic aneurysm patients - a proteomic approach.

OBJECTIVE: The aim of the study is to investigate the differential expression of proteins in serum of abdominal aortic aneurysm (AAA) patients in relation to aneurysm size (D(max)) and progression. METHODS: Two-dimensional differential in-gel electrophoresis (2D-DIGE) together with tandem mass spectrometry (MS/MS) was used to analyse the serum proteome from patients with small (D(max) 30-54 mm) AAA, either stable (increase D(max) <5 mm year⁻¹; n = 8) or progressive (increase D(max) ≥5 mm year⁻¹; n = 8), and large (D(max) ≥ 55 mm; n = 8) AAA. The identified proteins were quantitatively validated in a larger population (n = 80). RESULTS: Several proteins were differentially expressed in serum of small stable, small progressive and large AAA. Three validated proteins (immunoglobulin G (IgG), α1-antitrypsin (α1-AT) and Factor XII activity) showed strong correlation with D(max). Size combined with either Factor XII activity or α1-antitrypsin had minimal effect on the prognostic value in predicting aneurysm progression compared with size alone (area under the curve (AUC), 0.85; 95% confidence interval (CI), 0.73-0.97; p < 0.001 and AUC, 0.85; 95% CI, 0.72-0.98; p < 0.001 vs. AUC, 0.83; 95% CI, 0.71-0.96; p < 0.001, respectively). CONCLUSION: The present study indicates that both Factor XII and α1-antitrypsin are found in increased amounts in the serum of patients with expanding AAA. However, combination of either Factor XII or α1-antitrypsin with aneurysm diameter had little effect on prediction of aneurysm progression versus diameter alone.

The influence of wall stress on AAA growth and biomarkers.

OBJECTIVES: This study investigated the relation between abdominal aortic aneurysm (AAA) wall stress, AAA growth rate and biomarker concentrations. With increasing wall stress, more damage may be caused to the AAA wall, possibly leading to progression of the aneurysm and reflection in up- or downregulation of specific circulating biomarkers. Levels of matrix metalloproteinase-9, tissue inhibitor of matrix metalloproteinase-1, C-reactive protein and alpha 1-antitrypsin were therefore evaluated. METHODS: Thirty-seven patients (maximum AAA diameter 41-55mm) with two, three or four consecutive computed tomography angiography (CTA) scans were prospectively included. Diameter growth rate in mm/year was determined between each pair of two sequential CTA scans. AAA wall stress was computed by finite element analysis, based on the first of the two sequential CTA scans only (n=69 pairs). Biomarker information was determined in 46 measurements in 18 patients. The relation between AAA diameter and wall stress was determined and the AAA's were divided into three equally sized groups (relative low, medium and high stress). Growth rate and biomarker concentrations were compared between these groups. Additionally, correlation coefficients were computed between absolute wall stress, AAA growth and biomarker concentrations. RESULTS: A relative low AAA wall stress was associated with a lower aneurysm growth rate. Growth rate was also positively related to MMP-9 plasma concentration (r=0.32). The average MMP-9 and CRP concentrations increased with increasing degrees of relative wall stress, although the absolute and relative wall stress did not correlate with any of the biomarkers. CONCLUSION: Although lower relative wall stress was associated to a lower AAA growth rate, no relation was found between biomarker concentrations and wall stress. Future research may focus on more and extensive biomarker measurements in relation to AAA wall stress.