MIR-33 INHIBITORS AND USES THEREOF

摘要

The miRNA miR-33 is shown to inhibit the expression of carnitine O-octaniltransferase (CROT), Carnitine palmitoyltransferase 1A (CPT1a) and hydroxyacyl-CoA-dehydrogenase (HADHB), reduce fatty acid oxidation in hepatic cells, and target the insulin receptor substrate 2 (IRS-2) independent of its ability to elevating plasma high density lipoprotein (HDL) levels. MiR-33 inhibitors are also shown to increase cholesterol efflux from peripheral cells, such as cholesterol-laden macrophages present in atherosclerotic plaques. Compositions and methods are therefore provided for treating or preventing metabolic syndrome and atherosclerosis using miR-33 inhibitors. The miR-33 inhibitors are preferably antagomirs having a single-stranded nucleic acid sequence that is complementary to at least 12 contiguous nucleotides in miR-33 and therefore forms a duplex with miR-33 under physiological conditions.