Clinical implications for statin pleiotropy
Abstract
PURPOSE OF REVIEW: Atherosclerosis is a multi-factorial condition involving dyslipidemia that can result in cardiovascular disease. Statins are potent inhibitors of cholesterol biosynthesis, and in clinical trials, statins have been shown to be beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to occur much earlier and to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. SUMMARY OF FINDINGS: Recent studies indicate that some of the cholesterol-independent or 'pleiotropic' effects of statins involve improving endothelial function, enhancing the stability of atherosclerotic plaques, decreasing oxidative stress and inflammation, and inhibiting the thrombogenic response. Many of these pleiotropic effects are mediated by inhibition of isoprenoids, which serve as lipid attachments for intracellular signaling molecules. In particular, inhibition of small GTP-binding proteins, Rho, Ras, and Rac, whose proper membrane localization and function are dependent upon isoprenylation, may play an important role in mediating the pleiotropic effects of statins. SUMMARY: The potential clinical implications of statin pleiotropy suggests that perhaps other biomarkers, in addition to lipid levels, should be used to gauge the full efficacy of statin therapy in patients with cardiovascular risks or that statin therapy may be effective in disease states, such as inflammatory conditions, ischemic stroke or cancer, where elevated cholesterol levels have not been shown to be a strong epidemiological risk for these diseases.
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A research on statin drugs originated with the intention of developing new antimicrobial agents as the inhibition of HMG-CoA reductase results in the death of microorganisms.
“These finding are consistent with previous study, which revealed that a research on statin drugs originated with the intention of developing new antimicrobial agents as the inhibition of β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase, results in the death of microorganisms (Liao 2005).”
From In vitro study on the potential fungicidal effects of atorvastatin in combination with some azole drugs against multidrug resistant Candida albicans (2021) · cites this paper as Liao 2005
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Mahmoud, D. E., Faraag, A. H. I., & Abu El-Wafa, W. M. (2021) · World Journal of Microbiology and Biotechnology · doi:10.1007/s11274-021-03158-4 · Cited by 26 · see citing works
“These finding are consistent with previous study, which revealed that a research on statin drugs originated with the intention of developing new antimicrobial agents as the inhibition of β-Hydroxy β-methylglutaryl-CoA (HMG-CoA) reductase, results in the death of microorganisms (Liao 2005).”
Result
- Authors
- Liao, J. K.
- Affiliations
- Brigham and Women's Hospital (US)
- Corresponding author
- Liao, James K
- ORCID
- Liao, James K
- Venue
- Current Opinion in Lipidology
- Published
- 2005-12
- Volume
- 16
- Issue
- 6
- Pages
- 624-629
- ISSN
- 0957-9672 (ISSN-L)
- OpenAlex
- W2002676488
- Cited by
- 139
- References
- 70
- Citations by year
- 2026: 2 · 2025: 1 · 2023: 4 · 2022: 1 · 2021: 7 · 2020: 8 · 2019: 2 · 2018: 3 · 2017: 4 · 2016: 5 · 2015: 3 · 2014: 7 · 2013: 12 · 2012: 6
- FWCI
- 2.42
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Current Opinion in Lipidology (publishedVersion)
- PubMed (publishedVersion)
- Funders
- American Heart Association
- National Heart, Lung, and Blood Institute (HL 52233, R01HL052233)
- National Institute of Neurological Disorders and Stroke (NS10828)
- Topics
- Health Sciences › Medicine › Surgery › Lipoproteins and Cardiovascular Health
- Health Sciences › Medicine › Surgery › Cholesterol and Lipid Metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › Cancer, Lipids, and Metabolism
- Keywords
- statins, pleiotropy, atherosclerosis, endothelial function, plaque stability, oxidative stress, inflammation, thrombogenicity, Rho GTPases, Ras, Rac, cholesterol-independent effects, cardiovascular disease prevention, dyslipidemia
- MeSH terms
- Cholesterol, Humans, Risk Factors, Hydroxymethylglutaryl-CoA Reductase Inhibitors, Atherosclerosis
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