Hyperhomocysteinemia is associated with human coronary atherosclerosis through the reduction of the ratio of endothelium-bound to basal extracellular superoxide dismutase.

BACKGROUND

Homocysteine is involved in coronary atherosclerosis through oxidative stress, so the present study investigated the association between plasma concentrations of homocysteine and extracellular superoxide dismutase (EC-SOD) in coronary artery disease (CAD).

METHODS AND RESULTS

The study group comprised 154 consecutive male patients with suspected CAD who had undergone angiography. Plasma concentrations of homocysteine and EC-SOD, which was determined before (basal) and after heparin therapy, were measured and the difference was designated as endothelium-bound EC-SOD. The EC-SOD ratio (endothelium-bound/basal EC-SOD) was also evaluated as an index of binding capacity. The plasma homocysteine concentration in the stenosis (+) group (n=97, 12.0+/-4.6 micromol/L) was significantly higher than that of the stenosis (-) group (n=57, 10.2+/-3.0 micromol/L, p=0.004). Plasma homocysteine correlated positively with the basal EC-SOD (r=0.377, p<0.001) and negatively with the EC-SOD ratio (r=-0.199, p=0.014). When the group was subdivided according to either homocysteine or the EC-SOD ratio, there were 2 groups with high homocysteine concentration and of these atherosclerosis was reduced in the group with a high EC-SOD ratio.

CONCLUSIONS

In CAD patients, homocysteine is involved in the significant release of EC-SOD from the endothelium. Furthermore, the higher EC-SOD binding capacity, even at high concentrations of homocysteine, suggested that homocysteine-induced atherosclerosis was suppressed.