心肌梗死（MI）后心力衰竭是冠心病治疗难点，自体移植内皮祖细胞（EPC）能改善MI后心功能。高脂促EPC凋亡，降低移植存活率。我们已建立apoE-/-及HSP22-/-小鼠双敲除模型；发现HSP22对Ox-LDL诱导的EC及EPC损伤有保护作用,并以protein array筛选发现HSP22抑制CCL3,CCL5,CXCL12表达。本课题拟研究HSP22抗高脂诱导的EPC损伤机制。内容：1.体外培养WT、HSP22-/-和过表达小鼠EPC，抑制及过表达上述基因，Ox-LDL刺激，测EPC细胞凋亡、迁移及管腔形成能力；2.建立apoE-/-、apoE-/-和HSP22-/-双敲除小鼠高脂模型，测循环EPC数量及上述指标；3. 建立apoE-/-高脂及MI模型小鼠，分别移植WT、HSP22-/-和过表达小鼠EPC，测MI面积、心功能、新生血管密度。阐明上述问题为MI后心室重构防治提供新思路。

heart failure following myocardial infarction is the key in the coronary heart disease treatment. Autologous transplantation endothelial progenitor cell is able to alleviate heart function injury that caused by myocardial infarction.However, hyperlipidemia can induce endothelial progenitor cell apoptosis,which cause poor viability of transplanted cells. We successfully establish the ape and HSP22 double knock out mouse model. in the preliminary study, we already show that HSP22 can alleviate oxidative-LDL induced endothelial cell and endothelial progenitor cell through inhibit CCL3,CCL5,CXCL12 secretion. We plan to find out the mechanism further. The content include:1.we culture endothelial progenitor cell from WT、HSP22 knock out and over expression mouse, pretreat with CCL3,CCL5,CXCL12 inhibitor or over expression vector，then use Ox-LDL stimulate EPC, finally, we detect EPC apoptosis,tube formation and cell migration; 2.we establish hyperlipidmia model in the apoE knock out、apoE and HSP22 double knock out mosue, then detect circulating EPC,EPC apoptosis,tube formation and cell migration;3.We establish both hyperllipidmia and acute myocardial infarction model in the apoE knock out mouse, then those mice receive EPC transplantation from WT、HSP22 knock out and HSP22 overexpression mice. we detect myocardial infarction area, heart function and capillary density eventually. We will find a new pathway to prevent and treat ventricular remolding following myocardial infarction