Evaluation of neopterin levels and kynurenine pathway in patients with acute coronary syndrome (original) (raw)
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Relation of Kynurenine/Tryptophan with Immune and Inflammatory Markers in Coronary Artery Disease
SUMMARY Background: Inflammation and immune activation have a crucial role in the pathogenesis of cardiovascular diseases. Indolamine 2,3-dioxygenase, a tryptophan catabolising enzyme, is up-regulated with various inflammatory stimuli. The aim of this study was to evaluate the relationship of tryptophan degradation with immune and in-flammatory markers in coronary artery disease. Methods: 57 subjects undergoing coronary angiography were recruited. 18 subjects with normal coronary arteries according to Gensini scoring were selected as a control group and the rest of subjects were included in patient group. Serum tryptophan and kynurenine levels were determined with HPLC-UV method, and kynurenine/tryp-tophan ratio was evaluated as IDO activity. Serum neopterin and myeloperoxidase activity were measured by ELISA method. Results: While the kynurenine/tryptophan ratio and neopterin levels were similar in both groups, the patient group had higher myeloperoxidase and hs-CRP levels than controls (p = 0.02, p = 0.002, respectively). The kyn-urenine/tryptophan ratio was correlated with neopterin in both groups (r = 0.389, p = 0.025; r = 0.683, p = 0.002, respectively) and with hs-CRP in patients (r = 0.637, p = 0.001). Also, neopterin levels were correlated with hs-CRP in patients (r = 0.755, p = 0.0001). Conclusions: Our results are in line with a role of inflammation in coronary artery disease. The study provides evidence that IDO activity is related with immune and inflammatory states. Also, the study was performed in a limited hospital-based population. Further studies are warranted in the larger groups.
International Journal of Cardiology, 2013
Background: Immune system activation is involved in atherosclerosis. Neopterin production and tryptophan catabolism through the kynurenine pathway, measured by the kynurenine-tryptophan ratio (KTR), are induced by interferon gamma, thus both are considered markers of cell mediated immune activation. This study prospectively investigated their predictive value on acute coronary events among Norwegian community-dwelling older adults without previous coronary heart disease. Methods: 1112 men and 1631 women, 71-74 years old were examined during 1997-99 as part of the Hordaland Health Study. They were followed until an acute coronary event (defined as unstable angina, non-fatal or fatal acute myocardial infarction or sudden death) or December 31, 2006. Kaplan-Meier hazard curves were constructed for quartiles of plasma neopterin and KTR. Cox proportional hazards models adjusted for sex, body mass index, smoking, hypertension, renal function and cholesterol were used to examine the relation between neopterin and KTR quartiles and the study endpoint. Results: Median (interquartile range) values were 8.6 (7.2-10.4) nmol/L for neopterin and 25.8 (25.3-31.1) nmol/ μmol for KTR. During the follow up, 265 participants had at least one acute coronary event. Increased baseline levels of plasma neopterin and KTR were associated with continuous increased risk of developing the study endpoint (P-values for trend b 0.001 and 0.019, respectively). Adjusted hazard ratios comparing the fourth quartile to the first were 1.65 (95% CI; 1.11-2.47; P=0.013) for neopterin and 1.57 (95% CI 1.03-2.39; P=0.036) for KTR. Conclusion: Plasma neopterin and KTR levels predict acute coronary events in older adults without previous coronary heart disease.
The role of neopterin in cardiovascular disease
Monaldi archives for chest disease = Archivio Monaldi per le malattie del torace / Fondazione clinica del lavoro, IRCCS [and] Istituto di clinica tisiologica e malattie apparato respiratorio, Università di Napoli, Secondo ateneo, 2007
Inflammation plays a key role in the initiation and progression of atherosclerosis but also in the pathophysiology of atheromatous plaque disruption and the development of acute coronary syndromes. Neopterin is a marker of inflammation and of immune system activation, it is synthesized by macrophages, that, once activated, release this substance. Indeed, in clinical evaluation of patients, measurements of plasma levels of neopterin are usually used to evaluate progression of viral infections, renal transplant rejection, severe systemic inflammatory diseases, nephritic syndrome and several autoimmune diseases. This mediator is able to induce a pro-atherothrombotic phenotype in cells of the coronary circulation. Recent data indicate that serum levels of neopterin are elevated in patients with coronary and peripheral artery disease and seem to be a prognostic marker for major adverse cardiovascular events. In particular, neopterin levels predict future major cardiac and vascular advers...
Immune activation and degradation of tryptophan in coronary heart disease
European Journal of Clinical Investigation, 2003
Background Inflammation and immune activation appear to be important in the pathogenesis of coronary heart disease (CHD). Cytokine interferon-γ, which is released during cell-mediated immune responses, induces indoleamine (2,3)-dioxygenase (IDO), an enzyme degrading tryptophan to kynurenine. Therefore, immune stimulation is commonly associated with an increased kynurenine to tryptophan ratio (kyn trp −1 ) indicative for activated indoleamine (2,3)-dioxygenase and a measurable decline of tryptophan.
Neopterin, CD4+CD28− lymphocytes and the extent and severity of coronary artery disease
International Journal of Cardiology, 2009
Objectives: Macrophages and pro-inflammatory CD3+CD4+CD28− T lymphocytes are involved in atherosclerotic plaque destabilization. Whether neopterin, a macrophage-specific activation-marker, and circulating CD3+CD4+CD28− cells are also related to the severity and extent of coronary artery disease (CAD) in stable patients is still unclear. Methods: Coronary angiograms of 30 patients with stable angina pectoris were graded using the Gensini severity and an extent score. Patients were grouped according to the median of each score. Lymphocyte subsets were determined by FACS analysis and neopterin by radioimmunoassay. Peripheral endothelial function of the brachial artery (FMD) shown to correlate with cardiovascular risk factors was evaluated using high-resolution ultrasound. Results: More extensive CAD was associated with increased neopterin levels (8.3 ± 3.3 vs. 5.5 ± 1.2 nmol/L, p b 0.001) and increased CD3+ CD4+CD28− cells (3.1 ± 1.6 vs. 2.0 ± 1.2%, p b 0.05). A high Gensini severity score was associated with increased neopterin levels (7.8 ± 2.7 vs. 6.3 ± 1.7 nmol/L, p b 0.05), but not with CD3+CD4+CD28− cells. Neopterin correlated with both the extent (r = 0.59, p b 0.001) and the Gensini score (r = 0.57, p b 0.003). FMD was not correlated with both scores. Conclusions: Neopterin and CD3+CD4+CD28− lymphocytes are associated with CAD extent in stable patients, thereby emphasizing the inherent role of inflammation in atherogenesis itself beyond plaque destabilization. Neopterin's correlation with CAD severity might be additionally useful in identifying patients eligible for revascularization procedures.
Procalcitonin, c-reactive protein and neopterin levels in patients with coronary atherosclerosis
Acta Cardiologica, 2005
Objective-Recent studies demonstrate that the serum inflammatory markers increase in patients with atherosclerosis. We aimed to assess whether a difference exists between patients with acute coronary syndrome and patients with stable angina pectoris in respect to serum neopterin, procalcitonin (PCT) and C-reactive protein (CRP) levels. Methods and results-A total of 52∞∞patientss (42∞∞male, 10∞∞female) who had atherosclerosis confirmed by angiography and were being followed up for an acute coronary syndrome were recruited and for control group, 45∞∞patients with stable angina pectoris (SA) (35∞∞male and 10∞∞female) who underwent coronary angiography, were examined. Serum concentrations of neopterin, CRP and PCT in the study group (acute coronary syndrome) were compared to control group (stable angina pectoris).The mean neopterin level of the study group was 22.47∞ ∞ ±∞ ∞ 2.93 nmol/l, the mean CRP level was 30.40∞ ∞ ±∞ ∞ 8.05∞ ∞ mg/l and the mean PCT level was 0.40∞ ∞ ±∞ ∞ 0.04∞ ∞ ng/ml. In control group these levels were 12.26∞∞±∞∞0.61∞∞nmol/l (p∞∞<∞∞0.05), 5.26∞∞±∞∞0.64∞∞mg/l (p∞∞<∞∞0.001) and 0.19∞∞±∞∞0.02∞∞ng/ml (p∞∞<∞∞0.001), respectively. Conclusion-In the presented study our results showed that these markers can be useful for the assessment of inflammation related to atherosclerosis.
Serum neopterin and complex stenosis morphology in patients with unstable angina
Journal of The American College of Cardiology, 2000
OBJECTIVESWe sought to assess the relation between serum neopterin concentration and complex coronary artery stenosis in patients with unstable angina.BACKGROUNDMonocyte activation is associated with acute atheromatous plaque disruption and acute coronary syndromes. Angiographically demonstrated complex coronary stenosis is often an expression of plaque disruption. Increased serum concentration of neopterin, a pterydine derivative secreted by macrophages after stimulation by interferon-gamma, has been observed in patients with acute coronary syndromes as compared with control subjects and patients with stable angina pectoris.METHODSWe studied 50 patients with unstable angina (32 men) who underwent coronary angiography after hospital admission. All coronary stenoses with ≥30% diameter reduction were assessed and classified as “complex” (irregular or scalloped borders, ulceration or filling defects suggesting thrombi) or “smooth” (absence of complex features). Serum neopterin levels were assessed within 24 h of hospital admission using a commercially available immunoassay (enzyme-linked immunosorbent assay kit, IBL, Hamburg, Germany).RESULTSThirty-nine patients were classified in Braunwald class IIIb, four in class IIb and seven in class Ib. The number of complex lesions per patient was 2.6 ± 1.8 (mean ± SD). The mean neopterin concentration was 7.76 ± 3.62 nmol/liter. A significant correlation was observed between neopterin serum concentration and the presence of complex coronary stenoses (r = 0.35, p = 0.015). Multiple regression analysis showed that serum neopterin (p < 0.0001) was independently associated with the number of complex lesions. Other variables associated with complex lesions were the number of vessels with ≥75% stenosis (p < 0.0001), plasma creatinine (p = 0.003), triglycerides (p = 0.014) and a history of unstable angina (p = 0.032).CONCLUSIONSSerum neopterin concentration is associated with the presence of angiographically demonstrated complex lesions in patients with unstable angina and may represent a marker of coronary disease activity.