REDOX STATUS AND PROTEIN-BINDING OF PLASMA HOMOCYSTEINE AND OTHER AMINOTHIOLS IN PATIENTS WITH EARLY-ONSET PERIPHERAL VASCULAR-DISEASE - HOMOCYSTEINE AND PERIPHERAL VASCULAR-DISEASE

Elevated total homocysteine (Hcy) in plasma is an independent risk fac tor for early-onset vascular disease in the coronary, cerebral, and pe ripheral arteries. Different forms of Hcy, and their relation to other aminothiols in plasma, have not been investigated in patients with va scular disease. We therefore investigated 65 patients (35 men and 30 w omen) operated on for peripheral arterial disease at <50 years of age and 65 age- and sex-matched control subjects. Total, reduced, oxidized , and protein-bound Hey, cysteine (Cys), and cysteinylglycine (CysGly) were measured 0 to 11 years (mean, 6 years) postoperatively, in the f asting state, and after a standard methionine loading dose that caused a transient increase in reduced, oxidized, and protein-bound Hey. All forms of Hey and Cys, except reduced Cys, were higher in fasting pati ents than fasting control subjects. A similar difference between the g roups was observed after methionine loading. The levels of most Hcy fo rms both during fasting and after methionine loading were related to s moking, but multivariate analysis showed that the difference between p atients and control subjects could not be explained by smoking alone. Notably, reduced Cys and the reduced/total ratio for Cys were signific antly higher in control subjects than in patients, both during fasting and after methionine loading. In both groups, the redox status and pr otein binding of the various aminothiols in plasma were interactive, a s demonstrated by positive correlations between their reduced/total ra tios and by a decrease in protein-bound Cys when protein-bound Hey was elevated during methionine loading. Serum folate and to a lesser degr ee serum cobalamin and vitamin B-6 were predictors of oxidized and pro tein-bound Hcy in some patients and control subject subgroups. Thus, r educed, oxidized, and protein-bound Hey are elevated and reduced Cys i s decreased in patients with peripheral arterial disease. Reduced Hcy acts as a pro-oxidant in vitro and is a possible atherogenic agent, wh ereas reduced Cys may be a protective agent as a part of the antioxida nt defense system. The protein binding and redox status of different p lasma aminothiols are interactive in a way suggesting ongoing redox cy cling and disulfide exchange reactions. Thus, Hcy is one component in a complex system.