5-Methyltetrahydrofolate Rapidly Improves Endothelial Function and Decreases Superoxide Production in Human Vessels
Top Cited Papers
- 12 September 2006
- journal article
- research article
- Published by Wolters Kluwer Health in Circulation
- Vol. 114 (11) , 1193-1201
- https://doi.org/10.1161/circulationaha.106.612325
Abstract
Background— The circulating form of folic acid, 5-methyltetrahydrofolate (5-MTHF), may have beneficial effects on endothelial function; however, its mechanisms of action remain uncertain. Decreased nitric oxide (NO) bioavailability and increased vascular superoxide production in vascular disease states are due in part to endothelial NO synthase (eNOS) uncoupling related to deficiency of the eNOS cofactor tetrahydrobiopterin (BH4), but whether this mechanism is important in human atherosclerosis and represents a rational therapeutic target remains unclear. We hypothesized that 5-MTHF would improve endothelial function by decreasing superoxide and peroxynitrite production and by improving eNOS coupling, mediated by BH4 availability. Methods and Results— Vascular superoxide/peroxynitrite production and vasomotor responses to acetylcholine and bradykinin were determined in saphenous veins and internal mammary arteries from 117 patients undergoing CABG. The effects of 5-MTHF were examined ex vivo (n=61) by inc...Keywords
This publication has 25 references indexed in Scilit:
- Tetrahydrobiopterin, but Not l -Arginine, Decreases NO Synthase Uncoupling in Cells Expressing High Levels of Endothelial NO SynthaseHypertension, 2006
- Stoichiometric Relationships Between Endothelial Tetrahydrobiopterin, Endothelial NO Synthase (eNOS) Activity, and eNOS Coupling in VivoCirculation Research, 2005
- S-Adenosylmethionine and 5-Methyltetrahydrofolate Are Associated With Endothelial Function After Controlling for Confounding by HomocysteineArteriosclerosis, Thrombosis, and Vascular Biology, 2005
- TetrahydrobiopterinTrends in Cardiovascular Medicine, 2004
- Folate Therapy and In-Stent Restenosis after Coronary StentingNew England Journal of Medicine, 2004
- Oxidative Stress and Cardiovascular InjuryCirculation, 2003
- Interactions of Peroxynitrite, Tetrahydrobiopterin, Ascorbic Acid, and ThiolsJournal of Biological Chemistry, 2003
- Mechanisms of Increased Vascular Superoxide Production in Human Diabetes MellitusCirculation, 2002
- Oxidation of Tetrahydrobiopterin by Peroxynitrite: Implications for Vascular Endothelial FunctionBiochemical and Biophysical Research Communications, 1999
- Validation of Lucigenin as a Chemiluminescent Probe to Monitor Vascular Superoxide as Well as Basal Vascular Nitric Oxide ProductionBiochemical and Biophysical Research Communications, 1999