Effect of folic acid treatment on endothelium-dependent vasodilation and nitric oxide-derived end products in hyperhomocysteinemic subjects
- PMID: 11343667
- DOI: 10.1016/s0002-9343(01)00696-9
Effect of folic acid treatment on endothelium-dependent vasodilation and nitric oxide-derived end products in hyperhomocysteinemic subjects
Abstract
Purpose: An elevated plasma homocysteine concentration is an independent risk factor for cardiovascular diseases. In this study, we tested the hypothesis that hyperhomocysteinemia induces endothelial dysfunction mediated, at least in part, through nitric oxide-dependent mechanisms and that folic acid supplementation improves endothelial function in hyperhomocysteinemic subjects.
Subjects and methods: Endothelial function was evaluated in healthy controls and hyperhomocysteinemic subjects by measuring plasma levels of the nitric oxide-derived end products nitrite and nitrate and by assessing vasodilatory responses in the skin microcirculation and forearm vasculature. In the subjects with hyperhomocysteinemia, these measurements were repeated after 6 weeks and 12 months of folic acid supplementation.
Results: Compared with healthy controls, hyperhomocysteinemic subjects had significantly lower median plasma levels of nitric oxide-derived end products (12.1 microM [range 4.4 to 41.8] versus 24.6 microM [13.6 to 53.2]; P <0.001), a significantly lower endothelium-dependent vasodilatory response to acetylcholine (P <0.01), hyperemic response in the microcirculation (P <0.01), and total forearm blood flow during reactive hyperemia (P = 0.01). There was no significant difference in the endothelium-independent response. Folic acid treatment for 12 months increased the plasma level of nitric oxide-derived end products by 121% (95% confidence interval [CI], 72% to 170%), the vasodilatory response to acetylcholine by 124% (95% CI, 36% to 212%), and the ischemia-mediated hyperemic responses in the microcirculation by 60% (95% CI, 25% to 96%) and in the forearm vasculature by 47% (95% CI, 21% to 73%).
Conclusions: Homocysteine appears to induce its atherogenic effect, at least in part, by depressing endothelial function, possibly through nitric oxide-dependent mechanisms. This effect can be reversed by folic acid supplementation.
Similar articles
-
Homocysteine and endothelial function in human studies.Semin Vasc Med. 2005 May;5(2):172-82. doi: 10.1055/s-2005-872402. Semin Vasc Med. 2005. PMID: 16047269 Review.
-
Clinical use and rational management of homocysteine, folic acid, and B vitamins in cardiovascular and thrombotic diseases.Z Kardiol. 2004 Jun;93(6):439-53. doi: 10.1007/s00392-004-0075-3. Z Kardiol. 2004. PMID: 15252738 Review.
-
Folic acid enhances endothelial function and reduces blood pressure in smokers: a randomized controlled trial.J Intern Med. 2002 Dec;252(6):497-503. doi: 10.1046/j.1365-2796.2002.01059.x. J Intern Med. 2002. PMID: 12472909 Clinical Trial.
-
Does folic acid decrease plasma homocysteine and improve endothelial function in patients with predialysis renal failure?Circulation. 2000 Aug 22;102(8):871-5. doi: 10.1161/01.cir.102.8.871. Circulation. 2000. PMID: 10952955 Clinical Trial.
-
Folic acid improves arterial endothelial function in adults with hyperhomocystinemia.J Am Coll Cardiol. 1999 Dec;34(7):2002-6. doi: 10.1016/s0735-1097(99)00469-6. J Am Coll Cardiol. 1999. PMID: 10588216 Clinical Trial.
Cited by
-
Common Variants in One-Carbon Metabolism Genes (MTHFR, MTR, MTHFD1) and Depression in Gynecologic Cancers.Int J Mol Sci. 2023 Aug 8;24(16):12574. doi: 10.3390/ijms241612574. Int J Mol Sci. 2023. PMID: 37628752 Free PMC article.
-
Association of Inflammatory Markers/Cytokines with Cardiovascular Risk Manifestation in Patients with Endometriosis.Mediators Inflamm. 2021 Oct 31;2021:3425560. doi: 10.1155/2021/3425560. eCollection 2021. Mediators Inflamm. 2021. PMID: 34754275 Free PMC article.
-
Homocysteine and Age-Related Central Nervous System Diseases: Role of Inflammation.Int J Mol Sci. 2021 Jun 10;22(12):6259. doi: 10.3390/ijms22126259. Int J Mol Sci. 2021. PMID: 34200792 Free PMC article. Review.
-
Homocysteine Induces Inflammation in Retina and Brain.Biomolecules. 2020 Mar 3;10(3):393. doi: 10.3390/biom10030393. Biomolecules. 2020. PMID: 32138265 Free PMC article.
-
Decreased serum L-arginine and L-citrulline levels in major depression.Psychopharmacology (Berl). 2017 Nov;234(21):3241-3247. doi: 10.1007/s00213-017-4712-8. Epub 2017 Aug 13. Psychopharmacology (Berl). 2017. PMID: 28803324
Publication types
MeSH terms
Substances
LinkOut - more resources
Full Text Sources
Medical