MKP-3是一种特异性的双磷酸酶分子，现阶段关于MKP-3对心血管系统作用的研究有限，而且机制不详。在血管组织，MKP-3主要在内膜表达。目前，我们专门构建了MKP-3条件性基因敲除（floxed）小鼠，与Tie2-Cre小鼠交配后得到内皮细胞特异性MKP-3敲除小鼠。初步的结果显示，内皮特异性MKP-3敲除小鼠在高血压手术后相比对照小鼠表现出较低的动脉血压；同时内皮特异性MKP-3敲除影响血管平滑肌细胞增殖及血管重塑相关分子的表达，包括MMP-9、ET-1和AngⅡ。并且，内皮特异性MKP-3敲除后FOXO1磷酸化水平明显升高。基于这些结果，我们设想内皮细胞MKP-3可能通过FOXO1影响高血压血管重塑。因此，本项目应用内皮细胞特异性MKP-3敲除小鼠，研究内皮细胞MKP-3与高血压血管重塑的关系，阐明MKP-3/FOXO1信号通路在其中的作用，为高血压的治疗提供新的理论依据及潜在靶点。

MKP-3 is a dual-specificity phosphatase. To date, few published study demonstrate the role of MKP-3 in the cardiovascular system and the underlying mechanisms have not been fully elucidated. In the vascular tissue, MKP-3 is mainly expressed in the endothelium. At present, we successfully create the MKP-3 condition KO mice (floxed mice) and generate the endothelial cell-specific KO mice after crossing these floxed mice with Tie2-Cre mice. The pilot data showed that endothelial cell-specific MKP-3 KO mice displayed lower aterial blood pressure after operational model of hypertension compared with littermate control mice. Further, endothelial cell-specific knockout of MKP-3 markedly affected the proliferation of vascular smooth muscle cells and the levels of factors related to vascular remodeling, including MMP-9, ET-1 and AngⅡ. Notably, we observed an increase of phosphorylation of FOXO1 after endothelial cell-specific knockout of MKP-3. Based on these results, we speculated that MKP-3 might regulate hypertensive vascular remodeling via FOXO1. Thus, the goal of this proposed study is to define the relationship between MKP-3 and vascular remodeling induced by hypertension by using the endothelial cell-specific MKP-3 KO mice. Also, we will elucidate the molecular mechanisms associated with MKP-3/FOXO1 signaling pathway, eventually providing novel theoretical basis and potential therapeutic targets about hypertension.