Abstract 5104: Enhanced Expression of Tumor Necrosis Factor Receptor-Associated Factors in Acute and Chronic Coronary Heart Disease Correlates with Circulating Inflammatory Markers
Background: Tumor necrosis factor (TNF)-associated factors (TRAFs) are adaptor proteins for the TNF and interleukin/toll-like receptor superfamily. We previously demonstrated involvement of TRAFs in pro-inflammatory functions in atheroma-associated cells as well as their over-expression in murine and human atheromata. In the present study we investigated 1) TRAF expression in patients with chronic and/or acute coronary heart disease (CHD) compared with controls and 2) whether TRAFs correlate with established circulating inflammatory markers.
Methods: 170 patients undergoing coronary angiography were categorized to the groups “no CHD” (n=38), “stable CHD” (n=96), and “acute coronary syndrome (ACS, n=36). Circulating plasminogen activator inhibitor type-1 (PAI-1), high sensitive C-reactive protein (hsCRP), soluble CD40L (sCD40L), and chemokine ligand 18 (CCL18) were assayed in plasma by ELISA. Expression levels of TRAF-1 to -7 were quantified in total blood RNA by quantitative RT-PCR.
Results: PAI-1 levels increased (p<0.05) from patients with no CHD (26.0±1.5ng/ml) to patients with stable CHD (28.1±1.0ng/ml) and patients with acute coronary syndrome (33.4±2.0ng/ml). Levels of hsCRP were elevated in the ACS group (10.8±2.5mg/dL) compared with patients without CHD (3.8±1.8mg/dL) and stable CHD (3.5±0.8mg/dL), while levels of sCD40L and CCL18 remained unchanged. Copy numbers of TRAF-1, and -2 significantly increased over the three groups (P<0.05). With the exception of TRAF-5, the expression of all TRAFs was significantly higher in the combined group of CHD and ACS compared to those without CHD (P<0.05). Similarly, all TRAFs except for TRAF-5 and TRAF-7 correlated with the inflammatory marker hsCRP (Spearman 0.21 to 0.33) but not with lipid profile. On multivariate analysis the differences in expression levels for TRAF-1 retained statistical significance after adjustment for age, gender, and inflammatory markers.
Conclusions: We demonstrate the novel association between several TRAFs and stable and acute coronary heart disease as well as with circulating levels of hsCRP. Our data suggest that TRAFs, in particular TRAF-1 may serve as clinical markers for inflammation and coronary heart disease.