Abstract 4172: Direct Effects of 5-methyl-tetrahydrofolate on Vascular Endothelium And Superoxide Production In Human Arteries And Veins
Background: 5-methyltetrahydrofolate (5MTHF), the circulating form of folic acid, reduces plasma homocysteine, but its direct effects on vascular function are unclear. We evaluated the direct effect of 5MTHF on endothelial function and superoxide (O2-) production in saphenous veins (SV) and internal mammary arteries (IMA) of patients undergoing CABG.
Methods: Vasomotor responses to acetylcholine (ACh) were evaluated ex-vivo in vessel segments from 35 patients at baseline and after 45 minutes incubation with 5MTHF 0, 1, 10 and 100 μM. Vascular O2- was measured by lucigenin chemiluminescence in paired samples of SV and IMA after incubation with 5MTHF 0, 1 10 and 100 μM. The direct O2-scavenging capacity of 5MTHF was quantified using a xanthine/xanthine oxidase system, in comparison with vitamin C as positive control.
Results. All the concentrations of 5MTHF similarly improved the vasomotor responses of SV to ACh (Fig a⇓). Whereas 5MTHF at high concentrations (100 μM) had direct O2- scavenging effect, no direct scavenging was observed with concentrations <10μM (Fig b⇓). Vitamin C was a direct O2- scavenger even at 1μM (Fig b⇓). 5MTHF decreased O2- in both SV and IMA (Fig c⇓) compared to control, although there was no difference in O2- production between vessels exposed to 1, 10 and 100μΜ5MTHF.
Conclusions. 5MTHF rapidly improves endothelial function and decreases O2- production in vessels from patients with CAD, by a mechanism other than the direct scavenging of O2- radicals. These data suggest that 5MTHF may have a direct effect on vascular function by modifying intracellular redox and improving NO bioavailability in human vessels.