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. 2017 Aug 3;121(4):354–367. doi: 10.1161/CIRCRESAHA.116.310529

Figure 3.

Figure 3.

MicroRNA-146a (miR-146a) in bone marrow (BM)–derived cells contributes to atherogenesis. A, Ldlr−/− mice lethally irradiated and given BM transplantation (BMT) from wild-type (WT BM) or miR-146a−/− (knockout [KO] BM) donors followed by high cholesterol diet (HCD) for 4 or 12 wk. B, Body weights of female mice after 12-wk HCD (n=5–7). Weights of male mice were also unchanged (not shown). C, Food consumption in mice (n=4 mice per cage). T0 is 12 wk of HCD. D, Percentage of Oil Red-O (ORO) regions per aortic arch measured by en face imaging after 4- or 12-wk HCD (n=9–11). Representative images of plaque burden in aortas of Ldlr−/− mice with WT BM (top) and KO BM (bottom) after 12-wk HCD are shown to the right. Aortic root and descending thoracic aorta analyses are shown in Online Figure IIIB and IIID. E, Circulating proinflammatory markers, soluble intercellular adhesion molecule-1 (sICAM-1), IL-6 (interleukin-6), and TNF-α (tumor necrosis factor-α), measured by ELISA of plasma samples (n=4–7). F, Time course of plasma cholesterol measurement in Ldlr−/− mice receiving WT or KO BM (n=4–7; 1 group of mice was used for weeks 0 and 4, and a separate group was used for week 12). G, FPLC (fast protein liquid chromatography) trace of cholesterol content of lipoprotein fractions from plasma after 12 wk of HCD (pooled analysis of 4 samples). H, Intrahepatic total cholesterol (TC), free cholesterol (FC), and triglycerides (TG) after 12-wk HCD (n=4). Fecal cholesterol levels after 12 wk of HCD (n=8). I, Expression of inflammatory genes, Sort1, and a macrophage marker (F4/80) from liver tissues. Shown is a heat map of quantitative reverse transcriptase-polymerase chain reaction data (n=4–8). Values are relative to the controls for each group, as indicated. *Significant difference in expression. J, TG measurements in the media of cultured primary mouse hepatocytes treated with recombinant mouse IL-6 for 6 h (n=4). K, The predicted miR-146a binding in the human and mouse SORT1 3′ UTR (untranslated region; above) and luciferase analyses in bovine aortic endothelial cells (BAECs; n=5). HDL indicates high-density lipoprotein; and Ldlr, low-density lipoprotein receptor.