[Role of mimecan in development of atherosclerosis induced by increased blood pressure variability].

To examine the changes of mimecan protein expression in development of atherosclerosis induced by sinoaortic denervation, and to explore the effects of mimecan knock down on the proliferation and migration of vascular smooth muscle cells. Methods: The animals were randomly divided into a sham group and a model group (n=8 in each group). The rat model of blood pressure variability was established by sinoaortic denervation, and the hemodynamic indexes were recorded 20 weeks after the surgery to confirm the success of the model. The thoracic aorta was excised and stained with immunohistochemistry to observe the pathological changes of smooth muscle tissues and the changes of mimecan expression. The mice vascular smooth muscle cells were isolated, and which were treated with mimecan siRNA to knock down the mimecan expression. The cell proliferation was observed by 5-ethynyl-2'-deoxyuridine (Edu) in corporation test and the changes of cell migration was observed by wound healing test. Results: Twenty weeks after sinoaortic denervation, the blood pressure variability in the model group was significantly increased compared with that in the sham group, suggesting the model was successfully established. In addition, the increased blood pressure variability in the model group promoted the proliferation and migration of the vascular smooth muscle cells in thoracic aorta, while the expression of mimecan protein was significantly decreased. In in vitro assays, the knock down of mimecan in mice vascular smooth muscle cells could promote the cell proliferation and migration. Conclusion: Mimecan plays a protective role in the development of sinoaortic denervation induced atherosclerosis through amechanism involving suppression of the proliferation and migration of vascular smooth muscle cells.目的：观察大鼠血压变异性增加诱导的动脉粥样硬化发展中mimecan蛋白的表达变化，以及小鼠胸主动脉平滑肌细胞敲减mimecan蛋白对细胞增殖和迁移的影响。方法：动物实验共分为假手术组和模型组，每组8只。通过大鼠去窦弓神经手术建立血压变异性升高的动物模型，20周后采用检测的血流动力学指标对模型进行验证。胸主动脉进行石蜡切片后，通过免疫组织化学观察血管平滑肌组织的病理学改变及mimecan蛋白的表达变化。原代分离培养小鼠胸主动脉平滑肌细胞。使用小干扰RNA敲减细胞mimecan蛋白，通过5-乙炔基-2'-脱氧尿苷掺入试验观察其对于细胞增殖的改变，通过划痕损伤试验观察其对于细胞迁移的改变。结果：手术20周后，与假手术组相比，模型组大鼠血压变异性参数明显升高，证明模型建立成功。同时，血压变异性增加促进了模型组大鼠胸主动脉中血管平滑肌细胞的增殖与迁移，而mimecan蛋白的表达却显著降低。敲减小鼠血管平滑肌细胞中mimecan蛋白，能显著促进细胞的增殖和迁移。结论：Mimecan蛋白对血压变异性增加诱导的动脉粥样硬化的潜在发展有重要的保护作用，其作用机制可能是通过抑制血管平滑细胞的增殖和迁移而延缓动脉粥样硬化的进程。.