The Role of Mast Cells in the Development and Progression of Atherosclerosis

Mast cells, traditionally recognized for their roles in allergy and host defense, have recently been implicated in the pathogenesis of atherosclerosis. Their strategic localization in vascularized tissues and capacity to release a wide array of bioactive mediators position them as crucial contributors to both early and advanced stages of plaque development. This review summarizes the current understanding of mast cell functions in vascular homeostasis and immunity, with a special focus on their mechanistic involvement in atherogenesis and their potential as therapeutic targets in atherosclerosis. We conducted a comprehensive literature review of experimental, preclinical, and clinical studies addressing mast cell biology in the context of atherosclerosis. Particular emphasis was placed on molecular mechanisms, mast cell-derived mediators, and emerging pharmacologic interventions. Mast cells promote key atherogenic processes, including endothelial dysfunction, low-density lipoprotein (LDL) retention, monocyte recruitment, foam cell formation, fibrous cap thinning, and plaque rupture. Mechanistically, this involves the release of proteases (chymase and tryptase), histamine, and proinflammatory cytokines (e.g., tumor necrosis factor-alpha (TNF-α) and interleukin-6 (IL-6)). Additionally, mast cells contribute to caspase-1-mediated IL-1β production, which activates NF-κB signaling cascades leading to enhanced inflammatory cytokine production and adhesion molecule expression. Therapeutic strategies targeting mast cell activation, degranulation, metabolic activity, and specific receptors have demonstrated efficacy in preclinical models. Emerging approaches include dual protease inhibitors, personalized therapies guided by mast cell phenotyping, and advanced delivery systems. Mast cells are significant drivers of atherogenesis and plaque destabilization. Targeting mast cell-specific pathways represents a promising avenue for therapeutic intervention in atherosclerosis and the prevention of acute cardiovascular events.