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首页> 外文期刊>Life sciences >Statin therapy influences endothelial cell morphology and F-actin cytoskeleton structure when exposed to static and laminar shear stress conditions
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Statin therapy influences endothelial cell morphology and F-actin cytoskeleton structure when exposed to static and laminar shear stress conditions

机译：当暴露于静态和层流剪切应力条件下时，他汀类药物疗法会影响内皮细胞形态和F-肌动蛋白细胞骨架结构

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Aims: To determine how statin drugs (3-hydroxy-3-methylglutaryl coenzyme A reductase inhibitors) affect endothelial cell (EC) shape and F-actin cytoskeleton arrangement in the presence of physiologically relevant wall shear stress (WSS) of 12.5 dyn/cm2. Main methods Human abdominal aortic endothelial cells (HAAECs) were cultured to a confluent monolayer within three dimensional tissue culture models and presheared for 6 h at 12.5 dyn/cm 2 within a continuous flow loop. Statins were added to the perfusion media and the perfusion was continued for a further 24 h. ECs were then analyzed for morphology and F-actin cytoskeleton arrangement using light microscopy and laser scanning confocal microscopy. Key findings ECs became rounded with a significantly higher shape index with the addition of 10 μM simvastatin under both static and flow conditions. F-actin cytoskeleton structure was disorganized and fragmented with statin treatment under static and flow conditions. Neither of these findings were observed with the addition of both simvastatin and 200 μM mevalonate, confirming regulation through the cholesterol biosynthesis pathway. Significance EC morphology and F-actin cytoskeleton arrangement are regulated through the cholesterol biosynthesis pathway and are therefore impacted by statin treatment. ECs treated with statins became rounded, which is usually associated with unhealthy cells in regions of the vasculature prone to developing atherosclerotic plaques.
机译：目的：确定在存在生理相关的12.5 dyn / cm2的壁切应力（WSS）的情况下，他汀类药物（3-羟基-3-甲基戊二酰辅酶A还原酶抑制剂）如何影响内皮细胞（EC）形状和F-肌动蛋白细胞骨架排列。 。主要方法在三维组织培养模型中，将人腹主动脉内皮细胞（HAAEC）培养至汇合的单层，并在连续流动回路中以12.5 dyn / cm 2预剪切6 h。将他汀类药物添加到灌注培养基中，并继续灌注24小时。然后使用光学显微镜和激光扫描共聚焦显微镜分析EC的形态和F-肌动蛋白细胞骨架排列。主要发现在静态和流动条件下，添加10μM辛伐他汀均可使EC的形状指数显着提高，从而使EC变圆。 F-肌动蛋白的细胞骨架结构被破坏，并在静态和流动条件下用他汀治疗。添加辛伐他汀和200μM甲羟戊酸酯均未观察到这些发现，这证实了通过胆固醇生物合成途径的调节作用。重要的EC形态和F-肌动蛋白的细胞骨架排列是通过胆固醇的生物合成途径来调节的，因此受到他汀类药物治疗的影响。用他汀类药物治疗的EC呈圆形，通常与脉管系统区域中不健康的细胞相关，这些区域倾向于形成动脉粥样硬化斑块。

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