Serum Levels of Thioredoxin Are Associated with Stroke Risk, Severity, and Lesion Volumes

Abstract

Oxidative stress increases serum thioredoxin (TRX), a redox-regulating protein with antioxidant activity recognized as an oxidative stress marker. The aim of this study was to assess the clinical significance of serum TRX levels in Chinese patients with acute ischemic stroke (AIS). From January 1, 2012, to December 31, 2013, all patients with first-ever acute ischemic stroke were recruited to participate in the study. Serum levels of TRX were assayed with solid-phase sandwich enzyme-linked immunosorbent assay (ELISA), and the severity of stroke was evaluated with the National Institutes of Health Stroke Scale (NIHSS) score on admission. The results indicated that the median serum TRX levels were significantly (P < 0.0001) higher in stroke patients as compared to normal cases [15.03 ng/mL (interquartile range (IQR), 10.21-32.42) and 8.95 ng/mL (6.79-11.05), respectively]. We found the serum TRX reflected the disease severity of AIS. There was a significant positive association between serum TRX levels and NIHSS scores (r = 0.476, P < 0.0001). After adjusting for all other possible covariates, TRX remained as an independent marker of AIS with an adjusted OR of 1.245 (95 % confidence interval (CI), 1.164-1.352; P < 0.0001). Based on the receiver operating characteristic (ROC) curve, the optimal cutoff value of serum TRX levels as an indicator for auxiliary diagnosis of AIS was projected to be 11.0 ng/mL, which yielded a sensitivity of 80.3 % and a specificity of 73.7 %, with the area under the curve at 0.807 (95 % CI, 0.766-0.847). Further, in our study, we found that an increased risk of AIS was associated with serum TRX levels ≥11.0 ng/mL (adjusted OR 6.99; 95 % CI, 2.87-12.87) after adjusting for possible confounders. Our study demonstrated that serum TRX levels at admission were associated with stroke severity and lesion volumes. Elevated levels could be considered as a novel, independent diagnosis marker of AIS in a Chinese sample.

Blood biomarkers for stroke: the role of thioredoxin in diagnosis and prognosis of acute ischemic stroke

“…Supporting our results, Nanetti and colleagues [32] found that changes in the generation of free radicals and as a result oxidative stress may play a role in the pathogenesis and extent of acute ischemic lesions. This is in accordance with Qi and colleagues' [15] and Wu and colleagues' [17] while Tieer and colleagues [18] found serum thioredoxin levels in patients with small infarction were not significantly different from those in the large infarction volume group.…”

“…Several studies reported a close relation between increased expression of thioredoxin and cell damage due to oxidative stress. Thioredoxin system is up regulated in postmortem examination of Alzheimer disease in human and after experimental middle cerebral artery occlusion in rats [16] We found that thioredoxin level was significantly higher in acute stroke patients compared to control group (p = 0.001).This finding is in accordance with the results of most of the studies which assessed thioredoxin as a marker of oxidative stress in acute ischemic stroke [15,17,18].…”

“…The conflict between the results of our study supported by the results of Qi and colleagues [15] and Wu and colleagues [17] on one hand and the results of Tieer and colleagues [18] on the other hand regarding the relation between thioredoxin level and stroke severity at presentation, volume of infarction, and functional out come after 3 months may be explained by the differences in timing of sampling (onset of symptom within 24 h versus 72 h). The median NIHSS score in our study was 10.6 and in Qi and colleagues' and Wu and colleagues' studies was 9 while in Tieer study of the population, the median score was only 4 points.…”

“…Also, Wu and colleagues [17] found that serum thioredoxin levels were higher in patients with unfavorable outcome compared with those in patients with a favorable outcome.…”

Serum CXCL12 Levels as a Novel Predictor of Future Stroke Recurrence in Patients with Acute Ischemic Stroke

“…Stroke risk is determined by using traditional risk factors and risk assessment tools [3]. In order to improve stroke risk assessment, researchers have studied the predictive value of lipoprotein (a) [4], thioredoxin [5], high-sensitivity C-reactive protein [6], and insulin-like growth factor I [7] as biomarkers. Early detection and control of risk factors is thought to be crucial in reducing the risk of stroke and providing effective care [8].…”