血管平滑肌细胞(VSMC)转化为成骨表型是动脉粥样硬化(AS)内膜钙化的重要环节，其具体机制不清。fractalkine及其受体CX3CR1诱导炎症细胞迁移，促进细胞因子释放，介导VSMC迁移及增殖，在AS病程中发挥重要作用。最近研究发现fractalkine/CX3CR1可促进骨前体细胞成熟分化。我们推测fractalkine/CX3CR1可能通过①激活JAK/STAT信号通路上调促钙化因子Runx2表达，②抑制抗钙化因子OPG表达，促进VSMC向成骨表型转化。为此本研究拟应用基因工程技术和ApoE-/-/CX3CR1-/-基因敲除鼠验证fractalkine/CX3CR1在VSMC成骨表型转化和AS内膜钙化中的作用，明确fractalkine/CX3CR1作用下上述分子表达变化及对VSMC表型转化的影响。本研究旨在探讨AS中VSMC成骨表型转化的调控机制，寻找新的AS防治干预靶点。

Vascular smooth muscle cells (VSMC) differentiation to an osteogenic phenotype plays a critical role in the pathophysiology of atherosclerotic intimal calcification. However, its mechanism is not clear. The chemokine fractalkine/CX3CR1 mediates the interaction between the inflammatory cells and vascular wall cells, which plays an important role in the AS course. Recent studies have found that fractalkine/CX3CR1 can promote the maturation and differentiation of osteocyte precursor cells. We hypothesize that fractalkine/CX3CR1 promote the transformation of VSMC into osteogenic phenotype through ①activating JAK-STAT signaling pathway and up-regulating pro-calcification factor Runx2 expression, ②inhibiting anti-calcification factor OPG expression. The purpose of this research is to verify the effects of fractalkine/CX3CR1 in atherosclerotic intimal calcification and VSMC osteogenic phenotype transformation by gene engineering technology and ApoE-/-/CX3CR1-/- gene knockout mice; clarify the expressions of Runx2 and OPG in VSMC as well as their effect on VSMC osteogenic phenotype transformation under the action of fractalkine/CX3CR1; investigate the specific downstream signal transduction pathway under the action of fractalkine/CX3CR1 through inhibiting the expressions of CX3CR1, JAK and STAT. We intended to investigate the regulatory mechanism of VSMC osteogenic phenotype transformation in AS lesions and to seek a new target for AS prevention and treatment.