CXCR4 - a possible serum marker for risk stratification of abdominal aortic aneurysms.

Background: Abdominal aortic aneurysm (AAA) rupture is still associated with a mortality rate of 80-90%. Imaging techniques or molecular fingerprinting for patient-specific risk stratification to identify pending rupture are still lacking. The chemokine (C-X-C motif) receptor (CXCR4) activation by CXCL12 ligand has been identified as a marker of inflammation and atherosclerosis, associated with AAA. Both are highly expressed in the aortic aneurysm wall. However, it is still unclear whether different expression levels of CXCR4 and CXCL12 can distinguish ruptured AAAs (rAAA) from intact AAAs (iAAA). Patients and methods: Abdominal aortic tissue samples (rAAA: n=29; iAAA: n=54) were excised during open aortic repair. Corresponding serum samples from these patients (n=9 from rAAAs; n=47 from iAAA) were drawn pre-surgery. Healthy aortic tissue samples (n=8) obtained from adult kidney donors during transplantation and serum samples from healthy adult volunteers were used as controls (n=5 each). Results: CXCR4 was mainly expressed in the media of the aneurysmatic tissue. Focal positive staining was also observed in areas of inflammatory infiltrates within the adventitia. In tissue lysates, no significant differences between iAAA, rAAA, and healthy controls were observed upon ELISA analysis. In serum samples, the level of CXCR4 was significantly increased in rAAA by 4-fold compared to healthy controls (p=0.011) and 3.0-fold for rAAA compared to iAAA (p<0.001). Furthermore a significant positive correlation between aortic diameter and serum CXCR4 concentration was found for both, iAAA and rAAA (p=0.042). Univariate logistic regression analysis showed that increased CXCR4 serum concentrations were associated with AAA rupture (OR: 4.28, 95% CI: 1.95-12.1, p=0.001). Conclusions: CXCR4 concentration was significantly increased in serum of rAAA patients and showed a significant correlation with an increased aortic diameter. The level of CXCR4 in serum was associated with a more than 4-fold risk increase for rAAA and thus could possibly serve as a biomarker in the future. However, further validation in larger studies is required.

Evaluation of serum biomarkers for patients at increased risk of stroke.

Early recognition of vulnerable patients is an important issue for stroke prevention. In our study, a multiscore analysis of various biomarkers was performed to evaluate its superiority over the analysis of single factors. Study subjects (n = 110) were divided into four groups: asymptomatic patients with stable (n = 25) and unstable (n = 36) plaques and symptomatic patients with stable (n = 13) and unstable (n = 36) plaques. Serum levels of MMP-1, -2, -3, -7, -8, -9, TIMP-1, -2, TNF-α, IL-1b, and IL-6, -8, -10, -12 were measured. Multi-score analysis was performed using multiple receiver operating characteristics (ROC) and determination of appropriate cutoff values. Significant differences between the groups were observed for MMP-1, -7, -9 and TIMP-1 in serum of the study subjects (P < 0.05). Multiple biomarker analysis led to a significant increase in the AUC (area under curve). In case of plaque instability, positive predictive value (PPV) for up to 86.4% could be correctly associated with vulnerable plaques. Thus, multiscore analysis might be preferable than the use of single biomarkers.