Circulating miRNA in patients with non-alcoholic fatty liver disease and coronary artery disease.

Background: Non-alcoholic fatty liver disease (NAFLD) is the hepatic manifestation of metabolic syndrome and coronary artery disease (CAD) is the cardiac manifestation of metabolic syndrome. NAFLD is strongly linked to CAD and hepatic steatosis is an independent risk factor for CAD and cardiac mortality. The pathogenic mechanism underlying this association remains poorly understood. In this study, we explored expression of circulating microRNAs (miRNAs) in patients with NAFLD and associated CAD. Results: When compared to patients with NAFLD without CAD, patients with NAFLD and CAD had lower circulating levels of miR-132 (0.24 +/- 0.16 vs 0.30 +/- 0.11, p=0.03), while the circulating levels of miR-143 were higher (0.96 +/- 0.90 vs 0.64 +/- 0.77, p=0.02). The levels in circulation demonstrated trends opposite to previously observed intracellular levels in patients with CAD. In obese patients with NAFLD, lower circulating levels of miR-145 (1.42 +/- 1.00 vs 2.41 +/- 1.80), miR-211 (41.26 +/- 20.40 vs 57.56 +/- 25.45), miR-146a (2.13 +/- 1.40 vs 2.90 +/- 1.36) and miR-30c (6.92 +/- 4.99 vs 11.0 +/- 6.92) were detected when compared to lean patients with NAFLD. For miR-161 (0.59 +/- 1.19 vs 0.15 +/- 0.14) and miR-241 (0.28 +/- 0.29 vs 0.16 +/- 0.13), higher circulatory levels were detected in the obese patients with NAFLD. These observations suggest altered circulating levels of miRNAs that may serve to balance intracellular levels of miRNA in target tissues. Additional studies examining paired samples of target and producing tissues as well as respective plasma samples will help delineate the regulatory circuits governing the secretion and the uptake of miRNA in multitissue diseases.