ABCA1 expression and statins: inhibitory effect in peripheral blood mononuclear cells.
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.
Genvigir
Fabiana D V
FD
Department of Clinical & Toxicological Analysis, School of Pharmaceutical Sciences, University of Sao Paulo, Avenue Professor Lineu Prestes, 580, B.17, 05508-900, Sao Paulo, Brazil. fabidalla@usp.br
Hirata
Mario H
MH
Hirata
Rosario D C
RD
D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters / Q000235:genetics / Q000378:metabolism*; D000328:Adult; D016022:Case-Control Studies; D008076:Cholesterol, HDL / Q000096:biosynthesis; D015331:Cohort Studies; D005260:Female; D015870:Gene Expression / Q000187:drug effects*; D006579:Heterozygote; D006801:Humans; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors / Q000494:pharmacology*; D007963:Leukocytes, Mononuclear / Q000187:drug effects* / Q000378:metabolism; D050356:Lipid Metabolism / Q000235:genetics; D008055:Lipids / Q000097:blood; D008297:Male; D008875:Middle Aged; D020641:Polymorphism, Single Nucleotide; D011401:Promoter Regions, Genetic
C577836:ABCA1 protein, human; D064286:ATP Binding Cassette Transporter 1; D018528:ATP-Binding Cassette Transporters; D008076:Cholesterol, HDL; D019161:Hydroxymethylglutaryl-CoA Reductase Inhibitors; D008055:Lipids