Figure 2.

Reduced atherosclerosis in mice with global deletion of microRNA-146a (miR-146a). A, Schematic of high cholesterol diet (HCD) regimen for Ldlr^−/− and Ldlr^−/−;miR-146a^−/− (double knockout [DKO]) mice. B, Weights of male mice after 12- or 18-wk HCD (n=3–5). Weights of female mice were also unchanged between genotypes (not shown). C, Food consumption in mice (n=4 mice per cage). T₀ is 18 wk of HCD. D, Percentage of Oil Red-O (ORO) regions quantified from aortic arches of Ldlr^−/− and DKO mice after HCD for 12 or 18 wk. Representative images are shown to the right. The descending side of the aorta is to the right. Aortic root and descending thoracic aorta analyses are shown in Online Figure II. n=18 to 22 for 12-wk time point and n=4 for 18-wk time point. E, Circulating levels of proinflammatory markers, IL-6 (interleukin-6) and soluble intercellular adhesion molecule-1 (sICAM-1) in wild-type and DKO mice (n=5–8). F, Time course of plasma cholesterol measurements (n=3–5; 1 group of mice were used for weeks 1, 6, and 9, and a separate group was used for weeks 12 and 18). Mice were fasted overnight before sample collection. G, FPLC (fast protein liquid chromatography) trace of cholesterol content in lipoprotein fractions in plasma after 18 wk of HCD (pooled analysis of 5 samples). H, Intrahepatic cholesterol and triglyceride levels in mice after 12-wk HCD (n=13–14). Eighteen-week HCD is shown in Online Figure IID. Bile cholesterol (n=3) and fecal cholesterol (n=4) in mice after 18-wk HCD. I, Assessment of very-low-density lipoprotein (VLDL) secretion by measurement of triglycerides and cholesterol in plasma after injection of Poloxamer 407 (12-wk HCD; n=4, 2). Ldlr indicates low-density lipoprotein receptor.