The role of renal impairment in atherosclerotic inflammation

肾功能受损影响到很大比例的人群。它显著增加了死亡的风险，特别是由动脉粥样硬化引起的心脏病发作和中风等心血管疾病。动脉壁的慢性炎症、炎性白细胞的侵袭及其局部的增殖和分化是动脉粥样硬化发展的重要步骤。在肾病患者中，动脉粥样硬化的研究主要集中在血流动力学和矿物质代谢的改变上。肾损害中炎性血管白细胞浸润的机制尚未有系统的研究。我的初步数据显示，在动脉粥样硬化和肾脏损害中，白细胞，特别是髓细胞增加。这项拟议的项目将检验白介素17在肾脏损伤中参与动脉粥样硬化增强的机制的假说。IL-17对单核细胞和巨噬细胞的血管渗透、分化和增殖的影响将在体外和肾功能受损的小鼠动脉粥样硬化模型中进行测试。将对全球和细胞特异性的IL-17和IL-17受体缺陷小鼠进行研究。结果可能会确定导致肾功能受损的动脉粥样硬化性炎症加重的机制，并有助于优化对这一大群心血管并发症高危患者的治疗。

Impaired renal function affects a large proportion of the population. It conveys a significantly increased risk of death, especially from cardiovascular diseases such as heart attacks and strokes that are caused by atherosclerosis. Chronic inflammation of the arterial wall, invasion by inflammatory leukocytes and their local proliferation and differentiation are important steps in atherosclerosis development. In patients with renal disease, atherosclerosis research has mostly focused on altered hemodynamics and mineral metabolism. The inflammatory vascular leukocyte infiltrate in renal impairment has not been systematically explored. My preliminary data show an increase in leukocytes, especially myeloid cells, in atherosclerosis and renal impairment. The proposed project will test the hypothesis that Interleukin 17 is mechanistically involved in enhanced atherosclerosis in renal impairment. The impact of IL-17 on vascular infiltration, differentiation and proliferation on monocytes and macrophages will be tested in vitro and in a murine atherosclerosis model with impaired renal function. Global and cell specific IL-17 and Il-17 receptor deficient mice will be investigated.The results could identify mechanisms responsible for aggravation of atherosclerotic inflammation in impaired renal function and help to optimize treatment for this large group of patients at high risk of cardiovascular complications.