CPNE7-derived peptides CDP4 and UG28 as pro-angiogenic factors for endothelial regeneration.

BACKGROUND AND PURPOSE: Efficient endothelial regeneration is fundamental to microcirculatory restoration and hard tissue repair. CPNE7 family peptides have previously been shown to regulate osteogenesis and chondrogenesis, however, their involvement in vascular reconstruction has not been explored. EXPERIMENTAL APPROACH: In this study, we investigated the effect of two peptides derived from CPNE7, CDP4 and UG28, on human endothelial cells in vitro, evaluating their influence on proliferation, migration, chemotaxis, capillary-like structure formation, and secretion of growth factors and cytokines. KEY RESULTS: UG28 demonstrated the strongest pro-angiogenic activity, enhancing EC proliferation, directional migration, and pseudocapillary network formation, while CDP4 also promoted migration and early vascular organization; neither peptide showed cytotoxicity nor induced immune activation, and both were compatible with chitosan matrices. CONCLUSION AND IMPLICATIONS: CPNE7-derived peptides-especially UG28-are potent and safe pro-angiogenic agents with high translational potential, and their compatibility with chitosan supports their applicability in next-generation regenerative therapies targeting endothelial and microvascular repair.