Abstract 3632: Vascular Homocysteine vs 5-Methyl-Tetrahydrofolate as Regulators of Vascular Redox and Endothelial Function in Human Vessels
Background: Increased plasma total homocysteine (tHcy) is related with increased systemic oxidative stress, while 5-MTHF administration improves endothelial function and vascular redox. We studied the impact of endogenous 5-MTHF and tHcy variability on vascular redox and nitric oxide bioavailability in human vessels.
Methods: Paired segments of internal mammary arteries (IMA) and saphenous veins (SV) were harvested from 218 pts undergoing CABG. Vasomotor responses of SVs to acetylcholine (Ach) and sodium nitroprusside (SNP) were determined ex-vivo. Superoxide (O2−) generation (±LNAME, ±NADPH) in IMAs and SVs was determined by lucigenin-enhanced chemiluminescence. Vascular 5-MTHF and tHcy were determined by HPLC.
Results: Low vascular 5-MTHF and high vascular tHcy were associated with higher vascular α2- in IMA (Fig. A and B⇓). Vascular 5-MTHF affected only LNAME-inhibitable O2− (Fig. C⇓), while tHcy affected only NADPH-stimulated O2− (Fig D⇓). In multivariate analysis 5-MTHF was an independent predictor of LNAME-inhibitable O2− in IMA (beta(SE)= 0.531(0.242),p=0.033), while tHcy was a predictor of only NADPH-stimulated α2-(beta(SE)= 2040(732), p=0.008). Importantly, vascular 5-MTHF (Fig E⇓) but not tHcy (Fig F⇓) was a determinant of vasorelaxations of SV to ACh.
Conclusions: Vascular 5-MTHF and tHcy, both affect vascular redox in humans. Vascular 5-MTHF is a regulator of eNOS coupling and NO bioavailability, while tHcy is a determinant of NADPH-oxidase activity in human vessels. These findings provide novel insights into the complex relationship between folates, homocysteine and vascular function.