Atorvastatin reduces intracellular and extracellular ROS levels within the atherosclerotic aortic arch.

<p>Female <i>Apoe</i>^<i>-/-</i> mice were fed Western diet to induce advanced atherosclerotic lesions in the aortic arch. Then, mice were treated with vehicle (DMSO) or oral atorvastatin (100 mg/kg per day) for 5 days. <i>(A)</i> ROS levels were analyzed in the aortic arch (red areas). <i>(B–D)</i> Atorvastatin treatment reduced intracellular <i>(B and C)</i> and extracellular ROS levels <i>(D)</i>. <i>(E and F)</i> Plasma cholesterol <i>(E)</i> and triglycerides <i>(F)</i> was reduced by atorvastatin and, to larger extent, by lipid lowering by diet. n = 6 in each group. **p<0.01 vs vehicle, *p<0.05 vs vehicle. One sample t-test (C and D). ANOVA with Dunnet’s test for multiple comparisons (E and F).</p

Intracellular ROS correlates with macrophage content and extracellular ROS with smooth muscle cell content in advanced atherosclerotic lesions Female <i>Apoe</i>^<i>-/-</i> mice were fed Western diet to induce advanced atherosclerotic lesions in the aortic arch.

<p>(<i>A)</i> Intracellular and extracellular ROS were analyzed in the aortic arch (red area) <i>(B)</i> Smooth muscle cell and macrophage content was quantified in the aortic arch by analyzing sections from 4 different levels. <i>(C)</i> Section stained for macrophages (CD68: blue) and smooth muscle cells (α-actin: red). <i>(D and E)</i> Smooth muscle cell content in lesions correlated with extracellular <i>(E)</i> but not intracellular ROS <i>(D)</i>. <i>(F and G)</i> Macrophage content in lesions correlated with intracellular <i>(F)</i> but not extracellular ROS <i>(G)</i>. Linear regression (n = 25). NS (non significant).</p

Lipid lowering by diet does not affect ROS levels within the atherosclerotic aortic arch Female <i>Apoe</i>^<i>-/-</i> mice were first fed Western diet to induce advanced lesions in the aortic arch.

<p>Then, lipids were lowered by switching to chow diet for five days. A control group was maintained on Western diet. <i>(A)</i> Intracellular and extracellular ROS were assessed in the atherosclerotic arch (red). <i>(B)</i> Lipid lowering by diet did not affect intracellular ROS. <i>(C)</i> Lipid lowering by diet did not affect extracellular ROS. NS—non significant. One sample t-test. n = 6 in each group.</p

Intracellular ROS increase before formation of atherosclerotic lesions in hyperlipidemic mice Female <i>Apoe</i>^-/- mice were fed either chow diet or Western diet.

<p><i>(A)</i> The descending thoracic aorta (delineated by dashed line) was relatively spared from atherosclerosis, even in mice fed Western diet. <i>(B)</i> In the descending thoracic aorta, Western diet increased extracellular ROS before formation of atherosclerotic lesions <i>(C)</i> Extracellular ROS levels, in contrast, were increased after formation of atherosclerotic lesions. n = 6–7 in each group. *p>0.05 vs chow diet, One way ANOVA with Dunnett’s multiple comparison test.</p

Atorvastatin does not affect extent of atherosclerosis, lesion cell composition or lesion inflammation Female <i>Apoe</i>^<i>-/-</i> mice were first fed Western diet to induce advanced lesions in the aortic arch.

<p>Then, mice were treated with vehicle (DMSO) or oral atorvastatin (100 mg/kg per day) for 5 days. <i>(A)</i> Atorvastatin did not affect lesion area in the aorta. <i>(B)</i> Atorvastatin did not affect lesion cell composition. <i>(C)</i> Atorvastatin did not affect mRNA levels of inflammatory mediators. n = 6 in each group. Student’s t-test.</p