The Endothelial CXCR Family in Vascular Health and Disease

ABSTRACT Endothelial cells (ECs) form the dynamic interface between blood and tissue, serving as key regulators of vascular homeostasis, inflammation, and repair. Among the molecular systems governing endothelial behavior, the C‐X‐C motif chemokine receptor (CXCR) family—originally characterized in immunology for its roles in leukocyte trafficking and immune signaling—has recently emerged as a pivotal regulator of vascular biology. Accumulating evidence indicates that CXCRs orchestrate endothelial development, angiogenesis, and injury responses through context‐dependent signaling mechanisms. This review integrates recent advances in endothelial CXCR research, highlighting their molecular functions and translational relevance. We first describe the developmental and homeostatic subgroup in which CXCR4 and its atypical partner CXCR7/ACKR3 coordinate vascular morphogenesis and regeneration. In parallel, we contrast the proangiogenic ELR + receptors (CXCR1 and CXCR2) with the angiostatic ELR − receptor CXCR3 and discuss the emerging roles of CXCR5 and CXCR6 in linking chronic inflammation and adaptive immunity to vascular dysfunction. Collectively, these findings position the CXCR family as an integrated network that fine‐tunes endothelial phenotype and vascular fate, revealing new opportunities for precision therapeutic intervention.