Indoleamine 2,3 dioxygenase (IDO) as a new predictor for advance coronary artery diseases

Abstract

Background Indoleamine 2,3 dioxygenase (IDO), the rate-limiting enzyme in in the kynurenine (Kyn) pathway of tryptophan (Trp) degradation, is modulated by inflammation and regarded as a key molecule driving immunotolerance and immunosuppressive mechanisms. This response accelerates the resolution of inflamed tissues to protect them against collateral damage and facilitate tissue healing. A growing body of evidence indicates that IDO-mediated Trp metabolism is involved directly or indirectly in atherogenesis. Little is known about IDO activity in patients with active coronary artery disease (CAD). Purpose We hypothesized that IDO activity as reflected by Kyn/Trp ratio and Kyn levels correlated with coronary artery disease (CAD) severity and predicted 1-year major adverse cardiac events (MACE). Method We prospectively enrolled the patients whom underwent coronary angiography in our institute. We excluded the patients whom might have other non-cardiac causes of elevated inflammatory biomarkers such as rheumatoid arthritis, allergic asthma, and so on. Measurements of IDO, hs-troponin and hs-CRP levels were performed at baseline and IDO activity was monitored every 6 month at interval. Baseline demographic, coronary angiogram/interventions data were recorded. Significant CAD defined as >70% stenosis in major epicardial vessel. Patients were followed up for 1-year. MACE were pre-specified. Results Three-hundred and five patients were enrolled. Ninety-eight patients (32%) presented with acute coronary syndrome. There was a significant difference in IDO, kynurenine, and hs-troponin between patients with and without significant CAD (Table 1). In addition, baseline IDO activity, kynurenine and hs-troponin levels were significantly higher in significant CAD patients with 3-vessel, 2-vessel and 1-vessel involvements than those with insignificant CAD; (0.17 vs 0.14 vs 0.14 vs 0.04, p<0.01), (5.8 vs 4.5 vs 5.1 vs 2.9 μM/g, p<0.01) and (18.2 vs 12.4 vs 12.7 vs 11.1 mg/dL, p<0.001), respectively. Preliminary data in 287 patients with completion of 1-year follow up showed that 1-year mortality was 2.9%. In comparison between patients who survived and death, it demonstrated markedly higher baseline kynurenine (5.12 vs 0.54 μM/g, p<0.03) and IDO (0.15 vs 0.01, p<0.02) in the patients without 1-year mortality. Conclusion Immunometabolic response mediated through IDO function were enhanced in patients with CAD and correlated with the severity and extent of the disease. Patient with inadequate IDO response had a higher 1-year mortality. Funding Acknowledgement Type of funding source: Public Institution(s). Main funding source(s): The Siriraj grant for research development and medical education of the Faculty of Medicine Siriraj Hospital