Abstract 4172: Direct Effects of 5-methyl-tetrahydrofolate on Vascular Endothelium And Superoxide Production In Human Arteries And Veins

Abstract

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 (O 2 -) 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 O 2 - was measured by lucigenin chemiluminescence in paired samples of SV and IMA after incubation with 5MTHF 0, 1 10 and 100 μM. The direct O 2 -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 O 2 - scavenging effect, no direct scavenging was observed with concentrations <10μM (Fig b ). Vitamin C was a direct O 2 - scavenger even at 1μM (Fig b ). 5MTHF decreased O 2 - in both SV and IMA (Fig c ) compared to control, although there was no difference in O 2 - production between vessels exposed to 1, 10 and 100μΜ5MTHF. Conclusions. 5MTHF rapidly improves endothelial function and decreases O 2 - production in vessels from patients with CAD, by a mechanism other than the direct scavenging of O 2 - 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.