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<div><div><p><strong>BACKGROUND:</strong> microRNAs play pivotal roles in metabolism and other aspects of cell biology. microRNA-33 and liver X receptor (LXR) affect lipid metabolism and cholesterol trafficking. In this study, we evaluated effects of co-administration of miR-33 inhibitor and LXR activator on LXR-&alpha; and adenosine triphosphate-binding cassette transporter A1 (ABCA1) expression in mice liver.</p> <p><strong>METHODS:</strong> Twenty-four mice were randomly allocated into four groups (n = 6). Group 1 mice received standard chow diet without any treatment, group 2 received 30 mg/kg/48 hour LXR agonist (T0901317), group 3 received 1 mg/kg/48 hour in vivo locked nucleic acids (LNA) anti-miR-33 and group 4 received both T0901317 and in vivo LNA anti-miR-33. All treatments were administrated through intraperitoneal injection (IP). After 7 days and at the end of the study, mice were sacrificed, liver tissues were excised and blood samples were collected. LXR-&alpha; and ABCA1 genes and protein expression were quantified by real-time polymerase chain reaction (PCR) and western blotting, respectively.</p> <p><strong>RESULTS:</strong><strong> </strong>LXR activation caused LXR-&alpha; and ABCA1 mRNA (P &lt; 0.050) and protein elevation as compared to control (P &lt; 0.001). miR-33 inhibition attenuates T0901317 effect on LXR-&alpha; expression in group IV. Co-administration of T0901317 and anti-miR-33 remarkably elevated high-density lipoprotein cholesterol (HDL-C) levels, compared to control group (P = 0.001). Separate administration of T0901317 and anti-miR-33 also elevated HDL-C levels (P &lt; 0.010).</p> <p><strong>CONCLUSION:</strong> Co-administration of T0901317 and anti-miR-33 can be considered as a good therapeutic alternative for atherosclerosis because miR-33 inhibition reduced lipogenic effects of LXR-&alpha; activator and also helps LXR-&alpha; agonist to increase reverse cholesterol transport (RCT) and also HDL-C as antiatherogenic effects.</p> <p>&nbsp;</p></div><p>&nbsp;</p></div>