Secreted frizzled-related proteins in angiogenesis: molecular mechanisms and clinical implications

Angiogenesis, the formation of new blood vessels from pre-existing vasculature, is essential for tissue homeostasis, development, and repair. Dysregulation of this tightly regulated process contributes to a wide range of diseases, including cancer, ischemic disorders, and chronic inflammatory conditions. This review focuses on the secreted frizzled-related protein (SFRP) family, a group of pivotal yet underappreciated regulators of neovascularization. We discuss the tissue-specific expression patterns, regulatory mechanisms, and functional roles of SFRPs in both physiological and pathological vascular remodeling. Particular attention is given to their interactions with key signaling pathways, including Wnt, highlighting their context-dependent effects on angiogenesis. Drawing on extensive preclinical evidence, we position SFRPs as novel regulators of vascular remodeling and explore their potential as promising targets for therapeutic intervention. This comprehensive analysis underscores the importance of further mechanistic and clinical studies to unlock the therapeutic potential of SFRPs in vascular pathologies.