Mast cells in cardiovascular disease: fibrosis, angiogenesis and atherogenesis

Bueno, G.; Bot, I.; Kanhai, A.A.; Stilhano, R.; Libby, P.; Meyer, G.R.Y. de; Martin, L.

doi:doi:10.1016/j.pcad.2025.11.007

Mast cells have emerged as pivotal regulators of cardiovascular physiology and pathology, influencing key processes including fibrosis, angiogenesis, tissue regeneration, and atherosclerosis. This review synthesizes findings from 110 studies to delineate the multifaceted roles of mast cells across these domains. Historically associated with allergic responses, growing evidence now underscores their substantial contribution to the progression of cardiovascular diseases. In fibrotic remodeling, mast cells facilitate extracellular matrix deposition and fibroblast activation through the release of pro-fibrotic mediators such as tryptase and chymase. In the context of angiogenesis, mast cells enhance endothelial proliferation and vascular permeability, predominantly through VEGF-driven signaling pathways. Although the role of mast cells in cardiac regeneration remains underexplored, current evidence suggests a context-dependent function in modulating stem cell dynamics and inflammatory...Show moreMast cells have emerged as pivotal regulators of cardiovascular physiology and pathology, influencing key processes including fibrosis, angiogenesis, tissue regeneration, and atherosclerosis. This review synthesizes findings from 110 studies to delineate the multifaceted roles of mast cells across these domains. Historically associated with allergic responses, growing evidence now underscores their substantial contribution to the progression of cardiovascular diseases. In fibrotic remodeling, mast cells facilitate extracellular matrix deposition and fibroblast activation through the release of pro-fibrotic mediators such as tryptase and chymase. In the context of angiogenesis, mast cells enhance endothelial proliferation and vascular permeability, predominantly through VEGF-driven signaling pathways. Although the role of mast cells in cardiac regeneration remains underexplored, current evidence suggests a context-dependent function in modulating stem cell dynamics and inflammatory microenvironments. Additionally, mast cells can participate in the pathogenesis of atherosclerosis by promoting lipid accumulation, vascular inflammation, and plaque destabilization. Collectively, these findings highlight mast cells as integral components of cardiovascular disease mechanisms. Therapeutic targeting of mast cell-derived mediators and signaling pathways, through stabilizers, enzyme inhibitors, or selective modulators, represents an avenue worthy of investigation for clinical intervention. Future studies should refine these strategies, aiming to mitigate mast cell-driven pathogenesis while preserving their physiological roles in tissue homeostasis and immune defense.Show less

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Mast cells in cardiovascular disease: fibrosis, angiogenesis and atherogenesis