Increased plasma levels of homocysteine and other thiol compounds in rheumatoid arthritis women

Abstract

Objectives: Since moderate hyperhomocysteinemia is an independent risk factor for vascular disease and physiological thiol compounds mediate Cu 2+- and Fe 3+-dependent low-density lipoprotein (LDL) oxidation, we have studied the total plasma concentrations of thiol compounds including methionine as precursor of homocysteine in rheumatoid arthritis patients, in which the high mortality found is associated with cardiovascular disease. Design and methods: Thirty-eight women with rheumatoid arthritis and 25 age-matched control women were studied. Plasma was used to measure thiol compounds and amino acids by HPLC. Results: Rheumatoid arthritis patients showed significantly higher levels than healthy controls of total plasma homocysteine (17.3 ± 7.8 vs. 7.6 ± 1.9; p<0.001), cysteine (293 ± 61 vs. 201 ± 45; p < 0.001), cysteinglycine (32.7 ± 8.3 vs. 22.3 ± 4.7; p < 0.001) and methionine (25 ± 9 vs. 18 ± 3; p < 0.01), whereas total glutathione levels were not increased (4.7 ± 2.0 vs. 4.1 ± 1.6). Conclusions: The increased levels of thiol compounds found in rheumatoid arthritis patients may be implicated in the increased incidence of cardiovascular disease found in these patients by means of the toxic effect of homocysteine on endothelium and the increased susceptibility of LDL to oxidation by increased plasma amounts of thiol compounds such as cysteine.