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Webinar Advisory: Regulus to Host Discussion About Potential of microRNA-33 as Target for Treatment of Atherosclerosis
Date:10/24/2011

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About microRNA-33a/bmicroRNA-33a and b (miR-33a/b), which differ by only two nucleotides, are intronic microRNAs located  within the sterol response element binding protein genes SREBF2 and SREBF1, respectively, which code for transcription factors that regulate cholesterol homeostasis and fatty acid metabolism. Recent studies have shown that miR-33a/b regulates the cholesterol and fatty acid pathways in a negative feedback loop.  miR-33a/b represses the cholesterol transporter ABCA1 in hepatocytes and macrophages resulting in decreased cellular cholesterol efflux to apoA1, a key step in the generation of HDL-C and reverse cholesterol transport. Inhibition of miR-33 in mice, which only have miR-33a, resulted in an increase in expression of ABCA1 protein and increase in cholesterol efflux resulting in a reduction of atherosclerotic plaques (Rayner et al., J Clin Invest. 2011). In addition, miR-33a/b suppresses key enzymes involved in the oxidation of fatty acids resulting in the accumulation of triglyceride. Inhibition of miR-33a/b increases fatty acid oxidation and insulin signaling (Davalos et al., PNAS. 2011). These studies suggest that an anti-miR33a/b oligonucleotide treatment may be a promising strategy to treat atherosclerosis.  

About microRNAs The discovery of microRNA in humans during the last decade is one of the most exciting scientific breakthroughs in recent history. microRNAs are small RNA molecules, typically 20 to 25 nucleotides in length, that do not encode proteins but instead regulate gene expression. More than 700 microRNAs have been identified in the human
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