HMGB1 as a danger signal in vascular remodeling

Vascular function is determined by the structural and functional properties of the vascular wall, and accumulating evidence indicates that vascular inflammation is a central pathogenic mechanism underlying a wide spectrum of vascular diseases, including vascular remodeling characterized by structural alterations of the vessel wall. Despite advances in understanding the pathophysiology of vascular remodeling, its biological mechanisms remain complex and incompletely elucidated with respect to both causes and consequences. Emerging evidence supports a critical role for high mobility group box 1 (HMGB1) in the pathogenesis of vascular remodeling. Given its broad range of biological activities and its involvement in key processes of vascular pathology, HMGB1 has gained increasing attention as a potential therapeutic target. This review aims to elucidate the multifaceted role of HMGB1 in vascular remodeling, with particular emphasis on its contributions to vascular inflammation, cellular proliferation and migration, and extracellular matrix remodeling. We provide current mechanistic insights into the molecular signaling pathways activated by HMGB1 in vascular cells and discuss how these pathways contribute to maladaptive vascular remodeling. A deeper understanding of HMGB1-mediated pathways may advance our knowledge of vascular disease pathogenesis and facilitate the development of targeted therapeutic strategies aimed at modulating HMGB1-driven inflammation to prevent or reverse pathological vascular remodeling and its associated complications.