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Folate Improves Endothelial Function in Coronary Artery Disease: An Effect Mediated by Reduction of Intracellular Superoxide?
Open accessAbstract
Abstract —Homocysteine is a risk factor for coronary artery disease (CAD). Folic acid lowers homocysteine and may improve endothelial function in CAD, although the mechanism is unclear. We investigated the effect of folic acid on endothelial function, homocysteine, and oxidative stress in patients with CAD. We also examined the acute effect of 5-methyltetrahydrofolate (5-MTHF), the principal circulating folate, on endothelial function in vivo and on intracellular superoxide in cultured endothelial cells. A randomized crossover study of folic acid (5 mg daily) for 6 weeks was undertaken in 52 patients with CAD. Ten further patients were given intra-arterial 5-MTHF. Endothelial function was assessed by flow-mediated dilatation (FMD). Folic acid increased plasma folate ( P <0.001), lowered homocysteine by 19% ( P <0.001), and improved FMD ( P <0.001). FMD improvement did not correlate with homocysteine reduction. Malondialdehyde and total plasma antioxidant capacity, markers of oxidative stress, were unchanged. 5-MTHF acutely improved FMD ( P <0.001) without altering homocysteine ( P =0.47). In vitro, 5-MTHF abolished homocysteine-induced intracellular superoxide increase ( P <0.001); this effect was also observed with folic acid and tetrahydrobiopterin. Our data support the beneficial effect of folic acid on endothelial function in CAD but suggest that the mechanism is independent of homocysteine. Reduction of intracellular endothelial superoxide may have contributed to the effect.
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Citations
Cites
Folic Acid Reverts Dysfunction of Endothelial Nitric Oxide Synthase
Stroes, E. S. G., van Faassen, E. E., Yo, M., Martasek, P., Boer, P., Govers, R., & Rabelink, T. J. (2000) · Circulation Research · doi:10.1161/01.res.86.11.1129 · Cited by 285
Cited by
Antoniades, C., Shirodaria, C., Warrick, N., Cai, S., de Bono, J., Lee, J., Leeson, P., Neubauer, S., Ratnatunga, C., Pillai, R., et al. (2006) · Circulation · doi:10.1161/circulationaha.106.612325 · Cited by 365
DASH lowers blood pressure in obese hypertensives beyond potassium, magnesium and fibre
Al-Solaiman, Y., Jesri, A., Mountford, W. K., Lackland, D. T., Zhao, Y., & Egan, B. M. (2010) · Journal of Human Hypertension · doi:10.1038/jhh.2009.58 · Cited by 129
Wang, G., Hu, F. B., Mistry, K. B., Zhang, C., Ren, F., Huo, Y., Paige, D., Bartell, T., Hong, X., Caruso, D., et al. (2016) · JAMA Pediatrics · doi:10.1001/jamapediatrics.2016.0845 · Cited by 86
Metadata
- Authors
- Doshi, S. N., McDowell, I. F. W., Moat, S. J., Lang, D., Newcombe, R. G., Kredan, M. B., Lewis, M. J., & Goodfellow, J.
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2001-07
- Volume
- 21
- Issue
- 7
- Pages
- 1196-1202
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- OpenAlex
- W2105986115
- Cited by
- 248
- References
- 1
- FWCI
- 12.45
- Type
- journal article
- Language
- en
- Open access
- bronze
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- Doshi, S. N., McDowell, I. F. W., Moat, S. J., Lang, D., Newcombe, R. G., Kredan, M. B., Lewis, M. J., & Goodfellow, J. (2001). Folate Improves Endothelial Function in Coronary Artery Disease: An Effect Mediated by Reduction of Intracellular Superoxide? Arteriosclerosis, Thrombosis, and Vascular Biology. https://doi.org/10.1161/hq0701.092000
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Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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