"Critical limb ischemia (CLI) is a major health problem; it affects approximately three million people in Western Europe, its prevalence is increasing, adequate medical treatment is not available, and patients with advanced disease are usually unsuitable for revascularization procedures. Since CLI is characterized by inadequate tissue vascularization, much effort has been focused on strategies aimed at promoting neoangiogenesis. Emerging data suggest the clinical potential of vascular progenitor cells (PCs) to restore blood flow to the ischemic limb. Several factors have been shown to influence PC mobilization and homing to ischemic tissue. However, follow-up studies have yet to show long-term benefit. Therefore, the identification of novel molecules represents a major and clinically relevant task. One factor that mediates the cross-talk between PCs and a variety of cell types, including vascular cells, is stromal-derived factor 1 (SDF-1), which, through interaction with its receptor CXCR4 expressed on PCs, modulates PC role in angiogenesis. A key mediator of SDF-1/CXCR4 axis is Cyclophilin A (CyPA). Specifically, CyPA binds to CXCR4 and modulates SDF-1-mediated chemotactic cell migration. Further, CyPA has been shown to enhance endothelial cell (EC) proliferation as well as capillary-like structure development and migration. Importantly, our published data show that CyPA is crucial for the mobilization and recruitment of bone marrow (BM)-derived cells in the diseased aorta of ApoE-/- mice. However, CyPA role in PC function is unknown. Based on experimental evidences underlying the importance of CyPA in SDF-1/CXCR4 axis, ability to modulate EC function in vitro, and BM cell mobilization or recruitment, this proposal aims at evaluating the role of CyPA in new blood vessel development in response to ischemia. The elucidation of CyPA’s effect on PC functions may provide novel insights for the treatment of ischemic diseases and, specifically, CLI."