ABCA1 Expression and Statins: Inhibitory Effect in Peripheral Blood Mononuclear Cells

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.

KEYWORDS::

• ABCA1
• gene expression
• HDL
• mononuclear cells
• SNP
• statins

Acknowledgements

The authors thank Cristina M Fajardo, Simone S Arazi, Maria Alice V Willrich, Alice C Rodrigues, Raquel de Oliveira, Claudia Villazon, Nadia Preto Godoy, Verônica Simões de Oliveira and Helder Honorato Basques for their technical support. FDV Genvigir is a recipient of fellowship from FAPESP (FAPESP 2007/00398–3), Sao Paulo, SP, Brazil. MH Hirata and RDC Hirata are recipients of fellowships from CNPq, Brazil.

Financial & competing interests disclosure

The authors have no relevant affiliations or financial involvement with any organization or entity with a financial interest in or financial conflict with the subject matter or materials discussed in the manuscript. This includes employment, consultancies, honoraria, stock ownership or options, expert testimony, grants or patents received or pending, or royalties.

No writing assistance was utilized in the production of this manuscript.

Additional information

Funding

The authors thank Cristina M Fajardo, Simone S Arazi, Maria Alice V Willrich, Alice C Rodrigues, Raquel de Oliveira, Claudia Villazon, Nadia Preto Godoy, Verônica Simões de Oliveira and Helder Honorato Basques for their technical support. FDV Genvigir is a recipient of fellowship from FAPESP (FAPESP 2007/00398–3), Sao Paulo, SP, Brazil. MH Hirata and RDC Hirata are recipients of fellowships from CNPq, Brazil