Epigenetic Regulation of ATP-Binding Cassette Protein A1 (ABCA1) Gene Expression: A New Era to Alleviate Atherosclerotic Cardiovascular Disease

Abstract

The most important function of high density lipoprotein (HDL) is its ability to remove cholesterol from cells and tissues involved in the early stages of atherosclerosis back to the liver for excretion. The ATP-binding cassette transporters ABCA1 and ABCG1 are responsible for the major part of cholesterol efflux to HDL in macrophage foam cells. Thus, promoting the process of reverse cholesterol transport (RCT) by upregulating mainly ABCA1 remains one of the potential targets for the development of new therapeutic agents against atherosclerosis. Growing evidence suggests that posttranscriptional regulation of HDL biogenesis as well as modulation of ABCA1 expression are under the control of several genetic and epigenetic factors such as transcription factor (TFs), microRNAs (miRNAs) and RNA-binding proteins (RBPs).These factors may act either individually or in combination to orchestrate ABCA1 expression. Complementary to our recent work, we propose an exploratory model for the potential molecular mechanism(s) underlying epigenetic signature of ABCA1 gene regulation. Such a model may hopefully provide the basic framework for understanding the epigenetic regulation of RCT and contribute to the development of novel therapeutic strategies to alleviate the burden of cardiovascular diseases (CVD).

Keywords

• ABCA1
• HDL
• miRNA
• circular RNA
• gene expression
• RNA-binding proteins
• reverse cholesterol transport
• cardiovascular diseases