THE EFFECT OF FOLIC-ACID ON THE HOMOCYSTEINE METABOLISM IN HUMAN UMBILICAL VEIN ENDOTHELIAL-CELLS (HUVECS)

Mild hyperhomocysteinaemia is associated with increased risk for vascu lar disease. We studied homocysteine export from human umbilical vein endothelial cells (HUVECs) by measuring total homocysteine (tHcy) conc entrations in the culture medium, Under standard culture conditions tH cy concentrations in the HUVEC culture medium increased by constant am ounts after 24, 48 and 72 h [mean = 2 . 5 (SD +/- 0 . 7) mu mol L(-1) homocysteine every 24 h]. As the cells are the only source of homocyst eine increase in the culture medium, we designate this as homocysteine export from HUVEC. Folic acid supplementation to the culture medium l owered the homocysteine export in a dose-dependent manner. Methyl-tetr ahydrofolate (MeTHF) and folinic acid (a stable precursor of MeTHF) we re in this respect about 10 times more effective than folic acid. A 50 % reduction in the homocysteine export was seen with 10-30 nmol L(-1) MeTHF supplementation: reduction to almost zero was seen with 100-300 nmol L(-1) MeTHF, Additions to the culture medium of the other vitamin s involved in the homocysteine metabolism, such as vitamin B-12, vitam in B-6 and flavin adenine dinucleotide, did not show any effect on hom ocysteine export. Because homocysteine export reflects an imbalance in the homocysteine metabolism, our observations showed a susceptible de pendency of this metabolism on folic acid in endothelial cells.