Abstract
Background
Endothelial dysfunction of the coronary arteries caused by oxidative stress plays an important role in the pathogenesis of vasospastic angina pectoris (VSAP). Glutamate, a non-essential amino acid, exerts endothelial dysfunction by oxidative stress production through N-methyl-D-aspartate receptor activation. Besides oxidative stress, decrease of antioxidant may be responsible for endothelial dysfunction. Glutathione (GSH), an important antioxidant, is synthesized from imported cystine through the cystine/glutamate antiporter system (XC-) in association with the export of glutamate. Glutamate also competitively inhibits cystine import into the endothelial cells through the XC-leading to GSH depletion. Thus the extracellular glutamate and cystine are crucial for the intracellular redox status. However, it remains unclear whether glutamate and/or cystine are implicated in the pathogenesis of VSAP. As smoking induces powerful oxidant stresses in the whole body, we investigated plasma glutamate, cystine, oxidative stress markers and antioxidant capacity in non-smoker patients with VSAP.
Methods and results
Sixty-two consecutive non-smoker patients suspected having VSAP were performed coronary angiograms (CAG). Forty-nine patients who did not show any significant coronary stenosis (<50%) were performed the intracoronary acetylcholine provocation test. Patients were categorized into the VSAP-positive group (n=27) and the VSAP-negative group (n=22) on the basis of test results. Blood samples were collected from the femoral sheath before the CAG. Plasma glutamate, cystine, nitrotyrosine (NT), reactive oxygen metabolites (d-ROMs) and biological antioxidant potential (BAP) were measured. The levels of plasma glutamate and cystine in the VSAP-positive group were significantly higher than those in the VSAP-negative group (59.8±25.7 vs 43.5±18.7 nmol/L, p=0.0054, and 35.3±14.2 nmol/L vs 25.2±9.1 nmol/L, p=0.0018, respectively). The levels of plasma glutamate showed significant and positive association with the levels of plasma cystine (r=0.40, p=0.005). There were no significant differences in the levels of NT and d-ROMs as oxidative stress markers, and BAP as an antioxidant capacity between the two groups, respectively. However, the levels of plasma glutamate showed significant and negative association with BAP values (r=−0.3, p=0.038).
Conclusions
Plasma levels of glutamate were increased in non-smoker patients with VSAP and positively associated with plasma cystine levels and negatively associated with antioxidant capacity, suggesting that plasma glutamate modulate plasma cystine levels and antioxidant capacity through the XC- inhibition, and could be a novel risk factor of VSAP.
Urinary Biomarkers of Inflammation and Oxidative Stress Are Elevated in Obese Children and Correlate with a Marker of Endothelial Dysfunction
