GLUTATHIONE-RELATED ANTIOXIDANT DEFENSES IN HUMAN ATHEROSCLEROTIC PLAQUES

Background-Oxidative stress, resulting from an antioxidant/prooxidant imbalance, seems to be crucial in atherogenesis, Recent evidence has e merged, however, of a surprisingly high content of low-molecular-weigh t antioxidants in human atherosclerotic plaques, although other antiox idant systems have not been investigated in these lesions. Methods and Results-We studied glutathione-related antioxidant defenses (which pl ay a key role in tissue antioxidant protection) in carotid atheroscler otic plaques of 13 patients subjected to endarterectomy and in normal internal mammary arteries of 13 patients undergoing coronary artery by pass surgery. Selenium-dependent glutathione peroxidase activity was u ndetectable in the plaques of 7 patients; the other 6 patients with pl aques showed a mean enzymatic activity approximate to 3.5-fold lower t han that of mammary arteries. Glutathione reductase activity was also markedly lower in the plaques than in the arteries. Glutathione transf erase instead had comparable activity in the two tissues. Remarkably, 5 of the 7 patients with an undetectable selenium-dependent glutathion e peroxidase activity but none of the 6 with a detectable one were cha racterized by multivascular atherosclerotic involvement (3 patients) o r stenosis of the contralateral carotid artery (2 patients). Conclusio ns-A weak glutathione-related enzymatic antioxidant shield is present in human atherosclerotic lesions. Although the cause of this phenomeno n remains to be determined, the present data suggest that a specific a ntioxidant/prooxidant imbalance operative in the vascular wall may be involved in atherogenic processes in humans.