Oxidative Stress and Platelet Activation in Homozygous Homocystinuria

Background— Severe hyperhomocysteinemia due to cystathionine β-synthase deficiency (CβSD) is associated with early atherothrombotic vascular disease. Homocysteine may exert its effects by promoting oxidative damage. In the present study, we investigated whether in vivo formation of 8-iso-prostaglandin (PG) F2α, a platelet-active product of arachidonic acid peroxidation, is enhanced in CβSD and whether it correlates with in vivo platelet activation, as reflected by thromboxane (TX) metabolite excretion. Methods and Results— Urine and blood samples were obtained from patients with homozygous CβSD (n=13) and age-matched healthy subjects. Urinary 8-iso-PGF2α excretion was significantly higher in CβSD patients than in control subjects (640±384 versus 213±43 pg/mg creatinine; P=0.0015) and correlated with plasma homocysteine (ρ=0.398, P=0.0076). Similarly, urinary 11-dehydro-TXB2 excretion was enhanced in CβSD (1166±415 versus 324±72 pg/mg creatinine; P=0.0015) and correlated with urinary 8-iso-PGF2α (ρ=0.362, ...