The DOI matches its Crossref record; 68 of the 68 references it cites were found in a registry or an index.
Endothelial Nitric Oxide Synthase in Vascular Disease: From Marvel to Menace
Abstract
Nitric oxide (NO·) is an important protective molecule in the vasculature, and endothelial NO· synthase (eNOS) is responsible for most of the vascular NO· produced. A functional eNOS oxidizes its substrate l -arginine to l -citrulline and NO·. This normal function of eNOS requires dimerization of the enzyme, the presence of the substrate l -arginine, and the essential cofactor (6 R )-5,6,7,8-tetrahydro- l -biopterin (BH 4 ), one of the most potent naturally occurring reducing agents. Cardiovascular risk factors such as hypertension, hypercholesterolemia, diabetes mellitus, or chronic smoking stimulate the production of reactive oxygen species in the vascular wall. Nicotinamide adenine dinucleotide phosphate (NADPH) oxidases represent major sources of this reactive oxygen species and have been found upregulated and activated in animal models of hypertension, diabetes, and sedentary lifestyle and in patients with cardiovascular risk factors. Superoxide (O 2 · − ) reacts avidly with vascular NO· to form peroxynitrite (ONOO − ). The cofactor BH 4 is highly sensitive to oxidation by ONOO − . Diminished levels of BH 4 promote O 2 · − production by eNOS (referred to as eNOS uncoupling). This transformation of eNOS from a protective enzyme to a contributor to oxidative stress has been observed in several in vitro models, in animal models of cardiovascular diseases, and in patients with cardiovascular risk factors. In many cases, supplementation with BH 4 has been shown to correct eNOS dysfunction in animal models and patients. In addition, folic acid and infusions of vitamin C are able to restore eNOS functionality, most probably by enhancing BH 4 levels as well.
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In the citing paper
“The uncoupling causes eNOS activity to change from healthy (producing NO) to toxic (generating superoxide) (303).”
From Sources of Vascular Nitric Oxide and Reactive Oxygen Species and Their Regulation (2019) · cites this paper as [303]
In the citing paper
“Similarly, vascular disease, cardiovascular disease (CVD), and metabolic syndrome all share effective loss of NO function[23,35–39].”
From Enterosalivary nitrate metabolism and the microbiome: Intersection of microbial metabolism, nitric oxide and diet in cardiac and pulmonary vascular health (2017) · cites this paper as [23]
Citations
Cites
NAD(P)H Oxidase: Role in Cardiovascular Biology and Disease
Griendling, K. K., Sorescu, D., & Ushio-Fukai, M. (2000) · Circulation Research · doi:10.1161/01.res.86.5.494 · Cited by 2,886
Rajagopalan, S., Kurz, S. D., Münzel, T. F., Tarpey, M. M., Freeman, B. Α., Griendling, K. K., & Harrison, D. G. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118623 · Cited by 2,466
Heitzer, T., Schlinzig, T., Krohn, K., Meinertz, T., & Münzel, T. (2001) · Circulation · doi:10.1161/hc4601.099485 · Cited by 1,961
Hypercholesterolemia increases endothelial superoxide anion production.
Ohara, Y., Peterson, T. E., & Harrison, D. G. (1993) · Journal of Clinical Investigation · doi:10.1172/jci116491 · Cited by 1,765
Landmesser, U., Dikalov, S., Price, S. R., McCann, L., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci200314172 · Cited by 1,660
Landmesser, U., Dikalov, S., Price, S. R., McCann, L. A., Fukai, T., Holland, S. M., Mitch, W. E., & Harrison, D. G. (2003) · Journal of Clinical Investigation · doi:10.1172/jci14172 · Cited by 1,652
Mechanisms Underlying Endothelial Dysfunction in Diabetes Mellitus
Hink, U., Li, H., Mollnau, H., Oelze, M., Matheis, E., Hartmann, M., Skatchkov, M. P., Thaiss, F., Stahl, R. A. K., Warnholtz, A., et al. (2001) · Circulation Research · doi:10.1161/01.res.88.2.e14 · Cited by 1,190
Nitric oxide synthase isozymes. Characterization, purification, molecular cloning, and functions.
Förstermann, U., Closs, E. I., Pollock, J. S., Nakane, M., Schwarz, P., Gath, I., & Kleinert, H. (1994) · Hypertension · doi:10.1161/01.hyp.23.6.1121 · Cited by 1,110
Pollock, J. S., Förstermann, U., Mitchell, J. A., Warner, T. D., Schmidt, H. H. H. W., Nakane, M., & Murad, F. (1991) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.88.23.10480 · Cited by 979
Ting, H. H., Timimi, F. K., Boles, K., Creager, S. J., Ganz, P., & Creager, M. A. (1996) · Journal of Clinical Investigation · doi:10.1172/jci118394 · Cited by 869
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Research works printed but not linked: 23
- 10.1161/res.86.3.347 · DOI
- Li H Witte K August M Brausch I Gödtel-Armbrust U Habermeier A Closs EI Oelze M Münzel T Förstermann U. Reversal of eNOS uncoupling and upregulation of eNOS expression lowers blood pressure in hypertensive rats. J Am Coll Cardiol. In press.
- 10.1161/res.88.2.e14 · DOI
- 10.1161/circ.99.15.2027 · DOI
- 10.1161/res.86.5.494 · DOI
- 10.1161/circ.94.11.2756 · DOI
- 10.1161/circ.101.11.1261 · DOI
- 10.1161/circ.100.21.2131 · DOI
- 10.1161/hyp.30.1.57 · DOI
- 10.1161/res.77.3.510 · DOI
- 10.1161/circ.103.9.1282 · DOI
- 10.1161/hyp.33.6.1353 · DOI
- 10.1161/res.86.1.e7 · DOI
- 10.1161/res.86.2.e36 · DOI
- 10.1161/circ.104.10.1119 · DOI
- 10.1161/res.87.2.99 · DOI
- 10.1161/res.87.7.566 · DOI
- 10.1161/hyp.38.5.1044 · DOI
- 10.1161/circ.104.22.2673 · DOI
- 10.1161/circ.94.1.6 · DOI
- 10.1161/circ.97.3.237 · DOI
- 10.1161/atvb.22.1.6 · DOI
- 10.1161/atvb.20.1.185 · DOI
Cited by
Sorted by citations
Nitric Oxide and Peroxynitrite in Health and Disease
Pacher, P., Beckman, J. S., & Liaudet, L. (2007) · Physiological Reviews · doi:10.1152/physrev.00029.2006 · Cited by 6,390
Reactive Oxygen Species in Inflammation and Tissue Injury
Mittal, M., Siddiqui, M. R., Tran, K., Reddy, S. P., & Malik, A. B. (2014) · Antioxidants & Redox Signaling · doi:10.1089/ars.2012.5149 · Cited by 4,897
“Of these isoforms, only eNOS is the membrane-associated protein and is the predominant source of NO in vascular endothelial cells (121).”
Nanozymes: Classification, Catalytic Mechanisms, Activity Regulation, and Applications
Huang, Y., Ren, J., & Qu, X. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00672 · Cited by 3,572
Endothelial Function and Dysfunction: Testing and Clinical Relevance
Deanfield, J. E., Halcox, J. P., & Rabelink, T. J. (2007) · Circulation · doi:10.1161/circulationaha.106.652859 · Cited by 2,710
Reactive Oxygen Species (ROS)-Based Nanomedicine
Yang, B., Chen, Y., & Shi, J. (2019) · Chemical Reviews · doi:10.1021/acs.chemrev.8b00626 · Cited by 2,471
Metadata
- Authors
- Förstermann, U., & Münzel, T.
- Affiliations
- From the Departments of Pharmacology (U.F.) and Internal Medicine II (Cardiology) (T.M.), Johannes Gutenberg University Hospitals, Mainz, Germany.
- Venue
- Circulation
- Published
- 2006-04-04
- Volume
- 113
- Issue
- 13
- Pages
- 1708-1714
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2146190354
- Cited by
- 1,957
- References
- 67
- Citations by year
- 2026: 93 · 2025: 76 · 2024: 99 · 2023: 86 · 2022: 110 · 2021: 113 · 2020: 110 · 2019: 89 · 2018: 105 · 2017: 105 · 2016: 117 · 2015: 101 · 2014: 123 · 2013: 98 · 2012: 85
- FWCI
- 62.52
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiovascular Health and Disease Prevention
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Eicosanoids and Hypertension Pharmacology
- Keywords
- endothelial nitric oxide synthase, nitric oxide, tetrahydrobiopterin, eNOS uncoupling, NADPH oxidase, reactive oxygen species, superoxide, peroxynitrite, oxidative stress, cardiovascular risk factors, hypertension, hypercholesterolemia, diabetes mellitus, smoking, folic acid, vitamin C, L-arginine
- MeSH terms
- Animals, Endothelium, Vascular, Humans, Nitric Oxide, Vascular Diseases, Reactive Oxygen Species, Oxidative Stress, Nitric Oxide Synthase Type III
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