Decreased serum levels of thioredoxin in patients with coronary artery disease plus hyperhomocysteinemia is strongly associated with the disease severity

Objective: Elevation of homocysteine and thioredoxin (Trx) levels was found in some patients with coronary artery diseases (CAD). However, their correlations with CAD were not clear. Dysfunction of thioredoxin/thioredoxin reductase (TrxR) may cause oxidative stress that is common to CAD. We seek to determine the association among homocysteine, Trx/TrxR and CAD. Methods: Serum samples were collected from 150 CAD patients under statin treatment and 122 non-CAD controls. Risk factors for atherosclerosis including homocysteine, lipids and glucose levels were analyzed. Trx/TrxR activities and protein levels were determined using super-insulin assay and Western blot, respectively. One-way ANOVA, Tukey's post hoc test and Spearman's rank correlation coefficient were used for statistical analysis. CAD severity was evaluated by angiographic Gensini score. Results: Compared with non-CAD group, CAD group had significantly increased TrxR activity (P < 0.05) and homocysteine levels (P < 0.01), but not Trxactivity. After further dividing CAD group using homocysteine below 15 mu M asreference, Trx activity decreased significantly in CAD group with high homocysteine, and was inversely associated with homocysteine levels (r = -0.199, P < 0.05) that was, however, weakly positively associated with TrxR activity. Neither lipids nor glucose significantly affected Trx/TrxR activity. Association of CAD severity with low Trx plus high homocysteine was strong (r = -0.458, P < 0.001), but with high homocysteine alone was rather weak (r = 0.125, P = 0.225). Conclusion: In CAD patients, high homocysteine levels may cause low Trx activity, which is closely correlated to the extent and severity of CAD. (C) 2010 Elsevier Ireland Ltd. All rights reserved.