Deletion of the Mir-106b~?25 MicroRNA cluster attenuates atherosclerosis in Apolipoprotein E knockout mice

摘要

Abstract BackgroundMicroRNAs are short non-coding RNAs that regulate gene expression. The aim of this study was to gain an understanding of the possible role of the miR-106b~?25 microRNA cluster in regulating atherosclerosis in mice.MethodsMiR-106b~?25 knockout mice were outcrossed into Apolipoprotein E (ApoE) knockout background to generate double knockout mice. At 36?weeks of age, lesion size was evaluated in the aortic sinus by oil-red-O staining.ResultsLesion size was 2-fold smaller in double KO mice in comparison to ApoE KO mice . In addition, collagen staining showed a trend towards a stable plaque phenotype in the double KO mice. Lipid profiling of plasma samples of double KO and ApoE KO mice using FPLC revealed over 2-fold decrease in Very low density lipoprotein (VLDL) cholesterol content and a 50% decrease in low density lipoprotein (LDL) cholesterol content in double KO mice. By using target prediction software, we have identified several possible targets for the miR-106b~?25 cluster including the VLDL and LDL receptors. We found that upon feeding miR-106b~?25 KO mice with high fat diet, the expression of LDL and VLDL receptors was higher than in the wild-type mice, suggesting the miR-106b~?25 cluster regulates atherosclerosis by influencing clearance of VLDL and LDL from the plasma.ConclusionsWe identified the miR-106b~?25 cluster as a novel regulator of atherosclerosis in ApoE KO mice, presumably by regulating plasma cholesterol levels.