PLEIOTROPIC EFFECTS OF STATINS

Liao, James K.; Laufs, Ulrich

doi:10.1146/annurev.pharmtox.45.120403.095748

Cited by 1,994Lipoproteins and Cardiovascular HealthCholesterol and Lipid MetabolismCancer, Lipids, and Metabolism

PLEIOTROPIC EFFECTS OF STATINS

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Liao, James K., Laufs, Ulrich·2005·Annual Review of Pharmacology and Toxicology

DOI 10.1146/annurev.pharmtox.45.120403.095748PMC PMC2694580

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Abstract

▪ Abstract Statins are potent inhibitors of cholesterol biosynthesis. In clinical trials, statins are beneficial in the primary and secondary prevention of coronary heart disease. However, the overall benefits observed with statins appear to be greater than what might be expected from changes in lipid levels alone, suggesting effects beyond cholesterol lowering. Indeed, 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. Furthermore, statins have beneficial extrahepatic effects on the immune system, CNS, and bone. 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 on isoprenylation, may play an important role in mediating the pleiotropic effects of statins.

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Statins possess pleiotropic properties, such as improving endothelial function, reducing vascular inflammation, and stabilizing atherosclerotic plaques.
“Moreover, statins possess pleiotropic properties, such as improving endothelial function, reducing vascular inflammation, and stabilizing atherosclerotic plaques, which further support their role in mitigating residual risk [73].”
From Targeting triglycerides for cardiovascular risk reduction (2026) · cites this paper as [73]
Statins inhibit synthesis of important isoprenoids such as farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are lipid attachments for the γ subunit of heterotrimeric G-proteins, Ras, and Ras-like proteins.
“Thus, the effects of statins are connected with the inhibition of the synthesis of important isoprenoids, e.g.farnesyl pyrophosphate and geranylgeranyl pyrophosphate, which are important lipid attachments for the γ subunit of heterotrimeric G-proteins [12] , guanosine triphosphatebinding protein Ras, and Ras-like proteins (Rho, Rab, Rac, Ral, or Rap) [12][13][14] .”
From Statins as antifungal agents (2011) · cites this paper as [12]

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Authors: Liao, J. K., & Laufs, U.
Affiliations: Brigham and Women's Hospital (US)
Saarland University (DE)
ORCID: Liao, James K.
Laufs, Ulrich
Venue: Annual Review of Pharmacology and Toxicology
Publisher: Annual Reviews
Published: 2005-09-22
Volume: 45
Issue: 1
Pages: 89-118
ISSN: 0362-1642 (ISSN-L)
1545-4304
DOI: 10.1146/annurev.pharmtox.45.120403.095748
PMC: PMC2694580
OpenAlex: W2145653235
Cited by: 1,994
References: 195
Citations by year: 2026: 82 · 2025: 74 · 2024: 64 · 2023: 85 · 2022: 70 · 2021: 100 · 2020: 82 · 2019: 82 · 2018: 78 · 2017: 83 · 2016: 111 · 2015: 119 · 2014: 120 · 2013: 128 · 2012: 92
FWCI: 12.61
Type: journal article
Language: en
Open access: green
www.ncbi.nlm.nih.gov
Locations: The Annual Review of Pharmacology and Toxicology (publishedVersion)
PubMed (publishedVersion)
PubMed Central (acceptedVersion)
Funders: American Heart Association
National Heart, Lung, and Blood Institute (HL 52233, R01HL070274, R01HL052233, HL-48743, P01HL048743)
National Institute of Diabetes and Digestive and Kidney Diseases (R01DK062729)
National Institute of Neurological Disorders and Stroke (NS10828, F32NS010828, P50NS010828, P01NS010828)
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, cholesterol synthesis inhibition, coronary heart disease prevention, endothelial function, atherosclerotic plaque stability, oxidative stress, inflammation, small GTPases, Rho, Ras, Rac, immune system, central nervous system, bone
MeSH terms: Animals, Cardiovascular Diseases, Endothelium, Vascular, Humans, Hydroxymethylglutaryl-CoA Reductase Inhibitors

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