The DOI matches its Crossref record; 81 of the 82 references it cites were found in a registry or an index.
Effects of HMG-CoA Reductase Inhibitors on Endothelial Function: Role of Microdomains and Oxidative Stress
Open accessAbstract
Certain pleiotropic activities reported for 3-hydroxy-3-methylglutaryl coenzyme A (HMG-CoA) reductase inhibitors (statins) are related to reductions in cellular cholesterol biosynthesis and isoprenoid levels. In endothelial cells, these metabolic changes contribute to favorable effects on nitric oxide (NO) bioavailability. Given the essential role of NO in preserving vascular structure and function, this effect of statins is of considerable therapeutic importance. Statins have been demonstrated to restore endothelial NO production by several mechanisms, including upregulating endothelial NO synthase (eNOS) protein expression and blocking formation of reactive oxygen species. In this article, we will discuss additional ways in which statins restore endothelial NO production and improve endothelial function. (1) Statins modulate membrane microdomain formation, resulting in reduced expression of proteins that specifically inhibit eNOS activation. (2) Statins reduce sterol biosynthesis, thus interfering with the formation of pathologic microdomains, including cholesterol crystalline structures. This observation has important implications for plaque stabilization, as these microdomains contribute to cholesterol crystal formation and endothelial apoptosis. Finally, (3) statins improve endothelial function by interfering with oxidative stress pathways through both enzymatic and nonenzymatic mechanisms. The relationships between membrane microdomains, cholesterol biosynthesis, and endothelial function will be discussed.
Overview
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Integrity signals
Registry
Cites
Statistics
Verification
Claims the paper makes
The claims and statistics of this paper haven’t been checked yet.
Run the check — free, no account needed. It reads the open-access text and checks the sources it cites.
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
In the citing paper
“Statins and angiotensin type 1 receptor blockers have been shown to reduce oxidative stress and inflammation, improving endothelial function.”
In the citing paper
“Statins and angiotensin type 1 (AT-1) receptor blockers are widely used in preventing CVD and diabetic complications, and it has been suggested that many of their ancillary effects are due to strong intracellular antioxidant activity.”
In the citing paper
“Statins and AT-1 receptor inhibitors work as antioxidant in different ways.”
In the citing paper
“Statins and AT-1 receptor blockers protect endothelial function and reduce inflammation in diabetic and nondiabetic subjects, and these effects are convincingly mediated through their intracellular antioxidant activity.”
Self-check
Percentages, sums and reported differences re-computed from the paper’s own numbers.
The self-check needs the paper’s full text.
Citations
Cites
Atherosclerosis--an inflammatory disease
Ross, R. (1999) · New England Journal of Medicine · doi:10.1056/nejm199901143400207 · Cited by 21,725
Functional rafts in cell membranes
Simons, K., & Ikonen, E. (1997) · Nature · doi:10.1038/42408 · Cited by 9,757
Warren, Β. E. (1968) · Cited by 5,833
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
Structure and Function of Sphingolipid- and Cholesterol-rich Membrane Rafts
Brown, D. A., & London, E. (2000) · Journal of Biological Chemistry · doi:10.1074/jbc.r000005200 · Cited by 2,344
Molecular Bases of the Acute Coronary Syndromes
Libby, P. (1995) · Circulation · doi:10.1161/01.cir.91.11.2844 · Cited by 2,029
Regulatory Functions of the Vascular Endothelium
Epstein, F. H., Vane, J. R., Änggård, E., & Botting, R. M. (1990) · New England Journal of Medicine · doi:10.1056/nejm199007053230106 · Cited by 1,885
Upregulation of Endothelial Nitric Oxide Synthase by HMG CoA Reductase Inhibitors
Laufs, U., Fata, V. L., Plutzky, J., & Liao, J. K. (1998) · Circulation · doi:10.1161/01.cir.97.12.1129 · Cited by 1,837
Loss of Caveolae, Vascular Dysfunction, and Pulmonary Defects in Caveolin-1 Gene-Disrupted Mice
Dráb, M., Verkade, P., Elger, M., Kasper, M. E., Löhn, M., Lauterbach, B., Menne, J., Lindschau, C., Mende, F., Luft, F. C., et al. (2001) · Science · doi:10.1126/science.1062688 · Cited by 1,555
Cholesterol and the cell membrane
Yèagle, P. L. (1985) · Biochimica et Biophysica Acta (BBA) - Reviews on Biomembranes · doi:10.1016/0304-4157(85)90011-5 · Cited by 1,492
Research works printed but not linked: 18
- 10.1161/atvb.19.8.1891 · DOI
- 1991, FASEB J, 5, A531.
- 1992, Comments Mol Cell Biophys, 8, 53
- 10.1161/circ.101.11.1261 · DOI
- 1989, Am J Physiol, 257, H170
- 10.1161/res.69.1.2054935 · DOI
- 1995, J Membr Biol, 143, 51
- 10.1161/atvb.17.7.1337 · DOI
- 10.1161/circ.91.11.2844 · DOI
- 1989, Am J Pathol, 134, 705
- 10.1161/atvb.18.3.423 · DOI
- 10.1161/atvb.17.11.2975 · DOI
- 10.1161/circ.98.25.2822 · DOI
- 10.1161/circ.99.15.2027 · DOI
- 10.1161/res.86.5.494 · DOI
- 10.1161/circ.97.12.1129 · DOI
- 10.1161/atvb.20.1.61 · DOI
- 10.1161/atvb.22.2.300 · DOI
Cited by
Sorted by citations
Oxidative stress and diabetic cardiovascular complications
Jay, D., Hitomi, H., & Griendling, K. K. (2006) · Free Radical Biology and Medicine · doi:10.1016/j.freeradbiomed.2005.06.018 · Cited by 464
Pleiotropic Effects of Statins: Benefit Beyond Cholesterol Reduction?
Robinson, J. G., Smith, B., Maheshwari, N., & Schrott, H. G. (2005) · Journal of the American College of Cardiology · doi:10.1016/j.jacc.2005.05.085 · Cited by 409
Schulman, S. P., Becker, L. C., Kass, D. A., Champion, H. C., Terrin, M. L., Forman, S., Ernst, K. V., Kelemen, M. D., Townsend, S. N., Capriotti, A., et al. (2006) · JAMA · doi:10.1001/jama.295.1.58 · Cited by 357
Kruppel-Like Factor 2 as a Novel Mediator of Statin Effects in Endothelial Cells
SenBanerjee, S., Mir, S. S., Lin, Z., Hamik, A., Atkins, G. B., Das, H., Banerjee, P., Kumar, A., & Jain, M. K. (2005) · Circulation · doi:10.1161/circulationaha.104.525774 · Cited by 348
Ceriello, A., Assaloni, R., Da Ros, R., Maier, A., Piconi, L., Quagliaro, L., Esposito, K., & Giugliano, D. (2005) · Circulation · doi:10.1161/01.cir.0000165070.46111.9f · Cited by 298
Metadata
- Authors
- Mason, R. P., Walter, M. F., & Jacob, R. F.
- Affiliations
- From the Cardiovascular Division, Department of Medicine (R.P.M.), Brigham and Women’s Hospital, Harvard Medical School, Boston, Mass; and the Cardiovascular Research Group (R.P.M., M.F.W., R.F.J.), Elucida Research LLC, Beverly, Mass.
- Brigham and Women's Hospital (US)
- Venue
- Circulation
- Published
- 2004-06
- Volume
- 109
- Issue
- 21_suppl_1
- Pages
- II34-41
- ISSN
- 0009-7322 (ISSN-L)
- 1524-4539
- OpenAlex
- W2148580947
- Cited by
- 175
- References
- 82
- Citations by year
- 2026: 2 · 2025: 1 · 2024: 3 · 2022: 1 · 2021: 8 · 2020: 6 · 2019: 4 · 2018: 3 · 2017: 8 · 2016: 5 · 2015: 8 · 2014: 9 · 2013: 9 · 2012: 6
- FWCI
- 10.85
- Type
- journal article
- Language
- en
- Open access
- bronze
- doi.org
- Locations
- Circulation (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- Pfizer
- National Heart, Lung, and Blood Institute
- National Eye Institute
- Topics
- Health Sciences › Medicine › Physiology (medical) › Nitric Oxide and Endothelin Effects
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- statins, endothelial function, nitric oxide bioavailability, endothelial nitric oxide synthase, lipid rafts, cholesterol biosynthesis, terpenoids, cholesterol crystals, oxidative stress, reactive oxygen species, endothelial cell apoptosis, plaque stabilization
- MeSH terms
- Animals, Arteriosclerosis, Cholesterol, Crystallization, Endothelium, Vascular, Humans, Nitric Oxide, Oxidative Stress, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Membrane Microdomains
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
