Abstract 4010: Soluble TRAIL in Peripheral Blood is a Novel Marker for Acute Coronary Syndromes
Background: Apoptosis of vascular smooth muscle cells and endothelial cells in the fibrous cap is prone to plaque vulnerability. Recently, we found that CD4 T cells trigger the TRAIL/TRAIL receptor 2 (DR5) pathway and cause VSMC apoptosis in acute coronary syndrome (ACS). We also showed that activated plasmacytoid dendritic cells (pDC) produce INFα through TRL9 and amplify cytotoxic CD4 T cell functions by enhancing TRAIL expression. In this study, we examined whether soluble TRAIL (sTRAIL) in peripheral blood shows changes in ACS that may serve as predictive marker of vulnerable patients.
Methods and Results: The sTRAIL levels were measured by ELISA in 110 patients undergoing coronary angiography, including 90 ACS patients and 20 chest pain syndrome patients without apparent coronary atherosclerosis. Fresh CD4 T cells were isolated from the peripheral blood of patients. The sTRAIL levels were lower in ACS than in controls (P<0.001). CD4 T cells capable of inducing HUVEC apoptosis expressed high levels of TRAIL in ACS patients (P<0.03), and negatively correlated with the sTRAIL levels (R=0.372, P<0.02). To examine whether sTRAIL levels could be used as marker of vulnerable patients with ACS, we measured sTRAIL levels in the time course and compared them with CPK and TnT after onset of ACS. While CPK and TnT of acute myocardial infarction elevated in the acute phase and recovered after 3days, sTRAIL showed negative parallel changes. Meanwhile, sTRAIL showed the same changes in unstable angina without CPK and TnT elevation. The levels of sTRAIL more decreased in patients with multiple coronary artery stenosis than in that without coronary artery stenosis while the levels of hsCRP did not. Furthermore, given a cutoff value of 48.6pg/ml, sTRAIL was able to discriminate ACS from control groups with sensitivity of 62.4%, specificity of 85.0%, and area under the receiver-operating characteristic curve (AUC) of 0.736. In contrast, an hsCRP cutoff value of 1.25mg/l showed lower sensitivity (47.3%), specificity (77.8%), and AUC (0.597) for the diagnosis of ACS.
Conclusions: Monitoring of TRAIL levels in ACS patients with both acute myocardial infarction and unstable angina was found useful in predicting vulnerability in patients with vulnerable plaques.