Positive correlation between CD137 expression and complex stenosis morphology in patients with acute coronary syndromes

Abstract

Background: CD137, a member of the tumor necrosis factor receptor superfamily, has been reported to be expressed highly in patients with acute coronary syndromes. However, limited information is available on the relationship between CD137 expression and complex stenosis morphology in patients with acute coronary syndromes.

Methods: Our study included normal controls (n=50), patients with stable angina (SA) (n=80) and patients with acute coronary syndromes (ACS), including unstable angina (UA) (n=70) and acute myocardial infarction (AMI) (n=100). The expression of CD137 in peripheral monocytes was analyzed by flow cytometry. Serum soluble CD137 (sCD137), MMP-9 and MMP-3 levels were measured by enzyme-linked immunosorbent assay kit. All coronary stenoses with ≥50% diameter reduction were assessed by angiographic coronary stenosis morphology.

Results: Patients with ACS(n=170) showed a significant increase of CD137 [23.6±5.7 mean fluorescence intensity (MFI)] expression in peripheral monocytes compared with control (8.4±2.6 MFI) and SA group (7.9±2.1 MFI) (p<0.001). sCD137 also showed higher level in patients with ACS(30.2±8.7 ng/ml) than in control (6.2±1.8 ng/ml) and SA group (7.1±2.1 ng/ml) (p<0.001). Serum MMP-3 and MMP-9 in patients with ACS were 2-times greater than those in control and SA group. A positive correlation was found between MMP-9, MMP-3 and CD137 expression in peripheral monocytes as well as sCD137 levels. An obvious correlation was also observed between soluble or membrane-bound CD137 expression and complex coronary stenoses (r1=0.5548, r2=0.4652, and p<0.001). In the logistic regression model, the independent predictors of ACS were sCD137 (odds ratio 2.671, 95% CI 1.718-4.153, P=0.000), MMP-9 (1.431, 1.043-1.964, P=0.026) and MMP-3 (1.368, 1.038-1.817, P=0.018).

Conclusion: Patients with ACS showed significantly positive correlation between CD137 expression and complex coronary stenosis morphology. We speculate that the increased CD137 expression might represent or reflect an instability of atherosclerotic plaques in patients with ACS.