肾动脉狭窄（RAS）能够加速全身动脉粥样硬化进展，其原因除肾血流灌注不足、高血压及肾素系统激活外，尚存在其他未知的关键因素。我们在前期研究中应用小鼠模型发现：RAS诱导缺血肾脏炎症因子Oncostatin M(OSM)表达上调，导致血浆及动脉粥样斑块内OSM蛋白水平持续升高；进一步研究显示，动脉斑块平滑肌细胞层存在OSM特异性受体，体外实验证实OSM促进平滑肌细胞增殖及迁移。据此提出科学假说:RAS诱导肾脏内细胞上调表达分泌OSM，其通过对平滑肌细胞的作用，介导RAS加速动脉粥样硬化过程。课题拟在预实验结果基础上，采用腺相关病毒载体转染等手段改变小鼠体内OSM水平，体内验证OSM是RAS加速动脉粥样硬化的关键因子，并对OSM的产生机制及OSM通过作用于平滑肌细胞促进动脉粥样硬化的分子机制进行深入研究。本研究的实施有助于阐明RAS加速动脉粥样硬化的作用机制，并为寻找新的治疗靶点提供理论依据。

Renal artery stenosis(RAS) contributes to the acceleration of systemic atherosclerosis. Effects of pro-atherogenic stimuli persist possibly even after reestablishment of renal blood flow, independent of renal blood flow and hypertension. Microarray expression profile identified the inflammatory cytokine oncostatin M(OSM) was persistently over-expressed in ischemic kidney of a partial renal artery ligation model in ApoE-/-(RAS/ApoE-/-) mice. Studies showed increased expression of OSM in the plasma and aorta athroma of RAS/ApoE-/- mice and OSMRβ in smooth muscle cells（SMC） in aorta athroma. Further studies showed OSM promoted proliferation and migration of SMC in vitro. Consequently, OSM secreted by cells in ischemic kidney in RAS/ApoE-/- mouse model are hypothesized to accelerate the progression of atherosclerosis in remote aorta via SMC. Based on these data, studies will be conducted to investigate that, 1) whether OSM play a key role in RAS-accelerated atherosclerosis with mouse model; 2) mechanism of high expression of OSM induced by RAS;and 3) pro-atherosclerotic role and mechanism of OSM on SMC. The result will be helpful to find a novel mechanism, novel therapy and diagnosis strategy for RAS-accelerated atherosclerosis.