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PMID: 15822172 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S. Review

Pleiotropic effects of statins.

Annual review of pharmacology and toxicology ·Vol. 45 ·2005-00-00 ·Pages 89-118

Liao JK, Laufs U

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.

MeSH Terms
Animals Cardiovascular Diseases/drug therapy,metabolism Endothelium, Vascular/drug effects,metabolism Humans Hydroxymethylglutaryl-CoA Reductase Inhibitors/metabolism,pharmacology,therapeutic use
Chemicals
Hydroxymethylglutaryl-CoA Reductase Inhibitors
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Liao James K
Vascular Medicine Research, Brigham & Women's Hospital, Cambridge, Massachusetts 02139, USA. [email protected]
Laufs Ulrich
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Article Info
Journal
Annual review of pharmacology and toxicology
Abbr.
Annu Rev Pharmacol Toxicol
ISSN
0362-1642
DOI
10.1146/annurev.pharmtox.45.120403.095748
Email
[email protected]
Published
2005-00-00
Pages
89-118
Language
English
Region
United States
NLM ID
7607088
PMCID
PMC2694580
Subset
IM
Grants
NINDS NIH HHS · P01 NS010828 · United States
NIDDK NIH HHS · R01 DK062729-01A1 · United States
NHLBI NIH HHS · R01 HL070274-02 · United States
NHLBI NIH HHS · P01 HL048743 · United States
NINDS NIH HHS · P01 NS010828-330036 · United States
NIDDK NIH HHS · R01 DK062729-02 · United States
NHLBI NIH HHS · R01 HL052233-05 · United States
NHLBI NIH HHS · R01 HL070274-01 · United States
NINDS NIH HHS · NS-10828 · United States
NHLBI NIH HHS · R01 HL052233-07 · United States
NINDS NIH HHS · P50 NS010828 · United States
NINDS NIH HHS · F32 NS010828 · United States
NHLBI NIH HHS · HL-48743 · United States
NHLBI NIH HHS · R01 HL052233-06 · United States
NHLBI NIH HHS · R01 HL052233 · United States
NIDDK NIH HHS · R01 DK062729 · United States
NHLBI NIH HHS · R01 HL070274 · United States
NHLBI NIH HHS · R01 HL070274-03 · United States
NINDS NIH HHS · P50 NS010828-290036 · United States
NHLBI NIH HHS · HL-52233 · United States
External Links
PubMed source DOI: 10.1146/annurev.pharmtox.45.120403.095748 PMC Full Text View journal details
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