内皮祖细胞（EPC）在血管再生过程中起关键作用，但糖尿病导致外周EPC数量减少、成血管功能受损，其机制至今未明。前期研究发现，基质细胞衍生因子（SDF-1）受体CXCR7在EPC细胞膜上表达，单独介导SDF-1诱导的EPCs存活，并与另一受体CXCR4共同介导SDF-1诱导的增殖、粘附、跨内皮迁移和血管形成。预实验发现：db/db糖尿病小鼠EPC细胞CXCR7表达显著降低，伴随着凋亡和成血管功能受损；体外高脂处理EPCs同样导致CXCR7表达下降、凋亡和成血管功能受损；而上述条件下CXCR4表达均无显著变化。据此提出科学假设：CXCR7表达失调是糖尿病EPC数量减少和功能受损的关键机制，提高CXCR7的表达能有效增强糖尿病EPC的存活和成血管功能。本课题主要目标是系统评价CXCR7对EPC功能和糖尿病血管再生的影响，并解析其分子机制，为以CXCR7为靶点治疗糖尿病心血管并发症提供依据。

Utilization of endothelial progenitor cells (EPCs) is a promising novel therapeutic option for regeneration of diabetic ischemic tissues. But diabetes reduces EPCs number in circulation and impairs its angiogenic function. Stromal cell derived factor 1 (SDF-1) and its receptors CXCR4 and CXCR7 are extensively found to involve in migration, chemotaxsis, proliferation and differentiation of bone marrow EPCs. Our previous study demonstrated that SDF-1 receptor CXCR7 expresses on EPCs, solely mediates the survival and coordinately mediates the proliferation, adhesion, trans-endothelial migration and tube formation of EPCs induced by SDF-1. Our preliminary study further demonstrated that the expression of CXCR7 is significantly decreased on EPCs from db/db mice, which was accompanied by significant apoptosis and tube formation impairment; incubation EPCs with ox-LDL also reduced the expression of CXCR7, induced apoptosis and tube formation impairment; but no significant changes were observed in CXCR4 expression. Based on these novel findings, we HYPOTHESIZE that the dysregulation of CXCR7 expression plays a critical role in diabetes induced EPCs apoptosis and dysfunction, and upregulation of CXCR7 can reverse apoptosis and rescue angiogenic function of EPCs. The objective of this study is to systemically evaluate the effects of CXCR7 upregulation on angiogenic function of EPCs and dissect the underlying mechanism. This study is expected to provide experimental evidence for treatment of diabetic vascular diseases targeting CXCR7.