The DOI matches its Crossref record; 200 of the 201 references it cites were found in a registry or an index.
Pleiotropic Effects of Statins on the Cardiovascular System
Open accessAbstract
The statins have been used for 30 years to prevent coronary artery disease and stroke. Their primary mechanism of action is the lowering of serum cholesterol through inhibiting hepatic cholesterol biosynthesis thereby upregulating the hepatic low-density lipoprotein (LDL) receptors and increasing the clearance of LDL-cholesterol. Statins may exert cardiovascular protective effects that are independent of LDL-cholesterol lowering called pleiotropic effects. Because statins inhibit the production of isoprenoid intermediates in the cholesterol biosynthetic pathway, the post-translational prenylation of small GTP-binding proteins such as Rho and Rac, and their downstream effectors such as Rho kinase and nicotinamide adenine dinucleotide phosphate oxidases are also inhibited. In cell culture and animal studies, these effects alter the expression of endothelial nitric oxide synthase, the stability of atherosclerotic plaques, the production of proinflammatory cytokines and reactive oxygen species, the reactivity of platelets, and the development of cardiac hypertrophy and fibrosis. The relative contributions of statin pleiotropy to clinical outcomes, however, remain a matter of debate and are hard to quantify because the degree of isoprenoid inhibition by statins correlates to some extent with the amount of LDL-cholesterol reduction. This review examines some of the currently proposed molecular mechanisms for statin pleiotropy and discusses whether they could have any clinical relevance in cardiovascular disease.
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“Beyond the modification of blood lipid levels, in vitro and in vivo studies showed that statins exert beneficial cardioprotective pleiotropic effects [35, 36].”
From Established and Emerging Lipid-Lowering Drugs for Primary and Secondary Cardiovascular Prevention (2023) · cites this paper as [36]
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Cites
3 retracted
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Liakopoulos, O. J., Kuhn, E. W., Slottosch, I., Wassmer, G., & Wahlers, T. (2012) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008493.pub2 · Cited by 145
RetractedPreoperative statin therapy for patients undergoing cardiac surgery
Kuhn, E. W., Slottosch, I., Wahlers, T., & Liakopoulos, O. J. (2015) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008493.pub3 · Cited by 53
RetractedPreoperative statin therapy for patients undergoing cardiac surgery
Kuhn, E. W., Slottosch, I., Wahlers, T., & Liakopoulos, O. J. (2016) · Cochrane Database of Systematic Reviews · doi:10.1002/14651858.cd008493.pub4 · Cited by 21
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Rosuvastatin to Prevent Vascular Events in Men and Women with Elevated C-Reactive Protein
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Regulation of the mevalonate pathway
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Research works printed but not linked: 1
- 10.1056/NEJM199811053391902 · DOI · Paper page
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Mach, F., Baigent, C., Catapano, A. L., Koskinas, K. C., Casula, M., Badimon, L., Chapman, M. J., De Backer, G. G., Delgado, V., Ference, B. A., et al. (2020) · European Heart Journal · doi:10.1093/eurheartj/ehz455 · Cited by 8,961
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Self-citationDementia prevention, intervention, and care: 2024 report of the Lancet standing Commission
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The Role of Inflammation in Cardiovascular Disease
Henein, M. Y., Vancheri, S., Longo, G., & Vancheri, F. (2022) · International Journal of Molecular Sciences · doi:10.3390/ijms232112906 · Cited by 802
Metadata
- Authors
- Oesterle, A., Laufs, U., & Liao, J. K.
- Affiliations
- University of Chicago (US)
- Venue
- Circulation Research
- Published
- 2017-01-06
- Volume
- 120
- Issue
- 1
- Pages
- 229-243
- ISSN
- 0009-7330 (ISSN-L)
- 1524-4571
- PMC
- PMC5467317
- OpenAlex
- W2570787279
- Semantic Scholar
- a6f953b7ad2110e4c1c93c3e33f8539676113484
- Cited by
- 1,247
- References
- 201
- Citations by year
- 2026: 120 · 2025: 136 · 2024: 144 · 2023: 142 · 2022: 159 · 2021: 177 · 2020: 150 · 2019: 100 · 2018: 79 · 2017: 37
- FWCI
- 21.24
- Type
- journal article
- Language
- en
- Update notices
- correction (2018-09-27)
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Circulation Research (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Heart, Lung, and Blood Institute (R01HL136962, R01HL052233)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Lipoproteins and Cardiovascular Health
- Life Sciences › Immunology and Microbiology › Immunology › Atherosclerosis and Cardiovascular Diseases
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Biochemistry › Cholesterol and Lipid Metabolism
- Keywords
- statins, pleiotropy, cardioprotection, Rho kinase, NADPH oxidase, endothelial nitric oxide synthase, prenylation, atherosclerotic plaque stability, inflammation, platelet reactivity, cardiac hypertrophy, fibrosis, LDL cholesterol lowering
- MeSH terms
- Animals, Cardiovascular Diseases, Cardiovascular System, Clinical Trials as Topic, Humans, Cholesterol, LDL, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Genetic Pleiotropy
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