ABCA1 expression and statins: inhibitory effect in peripheral blood mononuclear cells

Pharmacogenomics. 2009 Jun;10(6):997-1005. doi: 10.2217/pgs.09.30.

Abstract

The ATP-binding cassette transporter A1 (ABCA1) has an essential role in the formation of nascent high-density lipoprotein particles and also participates in the cholesterol efflux from macrophages in the artery wall. Several substances, such as statins, or even gene variants are able to modulate ABCA1 expression. There is strong evidence that statin treatment downregulates the ABCA1 expression in nonloaded macrophages. Interestingly, in cholesterol-loaded macrophages, which are more relevant to atherogenesis, this effect is lost. We observed an inhibitory effect of atorvastatin in peripheral blood mononuclear cells of hypercholesterolemic individuals. Moreover, in these individuals, the ABCA1 -14C>T polymorphism was associated with high baseline gene-expression levels. Other studies are needed to evaluate how relevant these findings are to the formation of arterial foam cells in vivo.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters / genetics
  • ATP-Binding Cassette Transporters / metabolism*
  • Adult
  • Case-Control Studies
  • Cholesterol, HDL / biosynthesis
  • Cohort Studies
  • Female
  • Gene Expression / drug effects*
  • Heterozygote
  • Humans
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors / pharmacology*
  • Leukocytes, Mononuclear / drug effects*
  • Leukocytes, Mononuclear / metabolism
  • Lipid Metabolism / genetics
  • Lipids / blood
  • Male
  • Middle Aged
  • Polymorphism, Single Nucleotide
  • Promoter Regions, Genetic

Substances

  • ABCA1 protein, human
  • ATP Binding Cassette Transporter 1
  • ATP-Binding Cassette Transporters
  • Cholesterol, HDL
  • Hydroxymethylglutaryl-CoA Reductase Inhibitors
  • Lipids