Abstract
Statins are mainly known for their plasma cholesterol-lowering properties and are widely used for the prevention of cardiovascular diseases. They however also exert pleiotropic effects through a variety of mechanisms, among which several immunosuppressive effects that are unrelated to their cholesterol-lowering activity. Interestingly, there has been recent evidence of antiviral effects, including preliminary studies on the efficacy of statins against HIV-1. This paper more particularly focuses on the specific inhibition of the binding of leukocyte function-associated antigen-1 (LFA-1) to intercellular adhesion molecule (ICAM-1) by statins, independently of the inhibition of HMGCoA reductase. Targeting the statin-binding site within LFA-1 or regulating LFA-1 affinity by inhibiting prenylation of the small GTPases could prove useful to treat inflammatory, autoimmune diseases and possibly viral infections, including HIV-1.
Publication types
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Research Support, Non-U.S. Gov't
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Review
MeSH terms
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Animals
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Antiretroviral Therapy, Highly Active
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Antiviral Agents / pharmacokinetics
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Antiviral Agents / pharmacology*
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Binding Sites / drug effects
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Cholesterol / metabolism
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HIV Infections / drug therapy
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HIV Infections / metabolism
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HIV Infections / virology
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HIV-1 / drug effects*
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HIV-1 / physiology
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Humans
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacokinetics
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Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
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In Vitro Techniques
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Intercellular Adhesion Molecule-1 / drug effects
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Intercellular Adhesion Molecule-1 / metabolism
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Lymphocyte Function-Associated Antigen-1 / drug effects
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Lymphocyte Function-Associated Antigen-1 / metabolism
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Models, Biological
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Protein Binding / drug effects
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Virus Replication / drug effects*
Substances
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Antiviral Agents
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Hydroxymethylglutaryl-CoA Reductase Inhibitors
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Lymphocyte Function-Associated Antigen-1
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Intercellular Adhesion Molecule-1
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Cholesterol