Cardiac Mast Cells: Underappreciated Immune Cells in Cardiovascular Homeostasis and Disease

Studies with murine mast cells, combining single-cell transcriptomics, imaging, and functional assays, now provide validation of prior observations demonstrating that mast cells form a highly heterogeneous population of immune cells. Mast cells are strategically located in different sections of the human myocardium, coronary arterial wall, and aortic valves. In each location, the mast cells exert organ-specific functions. Recent studies have uncovered mechanisms by which mast cells in these locations may participate both in physiological and pathological processes. Activation of PAR-2 receptors on cardiomyocytes by mast cell tryptase following experimental myocardial infarction can exert a protective effect. Immunologically activated human myocardial mast cells produce both angiogenic (VEGF-A) and lymphangiogenic (VEGF-C) factors that, by inducing the formation of new blood vessels and lymphatic vessels, may provide the myocardial mast cells a contributory role in the prevention and healing of ischemic damage of the myocardium. Mast cells are multifarious immune cells with complex roles in tissue homeostasis and disease. They produce a plethora of mediators that play roles in inflammation, angiogenesis, lymphangiogenesis, and tissue remodeling. Recent insights into the heterogeneity of cardiac mast cell (CMC) subpopulations have renewed interest in their functional diversity in homeostasis and disease. They are located within the human heart in the myocardium, in atherosclerotic plaques, in the aortic valve, and in close proximity to nerves. Their plasticity enables different and even opposite functions in response to changing tissue contexts. These characteristics render CMCs intriguing, with a dichotomous role in protecting against, or accelerating, cardiovascular diseases. Future work should aim to identify CMC subsets, which could reveal novel therapeutic opportunities for cardiovascular disorders. Mast cells are multifarious immune cells with complex roles in tissue homeostasis and disease. They produce a plethora of mediators that play roles in inflammation, angiogenesis, lymphangiogenesis, and tissue remodeling. Recent insights into the heterogeneity of cardiac mast cell (CMC) subpopulations have renewed interest in their functional diversity in homeostasis and disease. They are located within the human heart in the myocardium, in atherosclerotic plaques, in the aortic valve, and in close proximity to nerves. Their plasticity enables different and even opposite functions in response to changing tissue contexts. These characteristics render CMCs intriguing, with a dichotomous role in protecting against, or accelerating, cardiovascular diseases. Future work should aim to identify CMC subsets, which could reveal novel therapeutic opportunities for cardiovascular disorders. the formation of new blood vessels initiated by vascular endothelial growth factors (VEGFs). narrowing of the heart’s aortic valve. atherosclerotic-prone apolipoprotein E-deficient mice. a protease stored within the secretory granules of mast cells. enhances the ability of antibodies to clear microbes and potentiates inflammation. a KIT-independent mast cell-deficient mouse model. anaphylatoxins, produced during complement activation; activate human cardiac and skin mast cells. cationic protein stored within the secretory granules of eosinophils, which activates human cardiac mast cells. covers the atherosclerotic plaque. vasoactive and proinflammatory mediator stored and released by mast cells. immunoglobulin associated with allergic disorders. IgE binds to FcεRI receptors present on mast cells and basophils. acute coronary syndrome caused by an allergic reaction. lipid mediators synthesized by activated mast cells. the formation of lymphatic vessels initiated by VEGF-C and VEGF-D. cationic protein stored within the secretory granules of eosinophils; activates human cardiac mast cells. DNA structures released by activated mast cells and decorated with proteins from cytoplasmic granules. Mas-related G protein-coupled receptor member X2 receptor expressed by human and rodent mast cells and activated by substance P. heart-specific inflammatory conditions. programmed death-1 (PD-1) is a key immune checkpoint receptor expressed on several immune cells (T and B cells and mast cells). PD-1 ligand; PD-L1 can be expressed on tumor cells and several immune cells, including mast cells. lipid mediator synthesized through the cyclo-oxygenase pathway by mast cells. the renin–angiotensin system plays a pivotal role in the homeostatic control of cardiovascular functions. the most important cytokine regulating mast cell growth and functions. proinflammatory neuropeptide that activates the Mas-related G protein-coupled receptor member X2 (MRGPRX2). a neutral serine protease stored within the secretory granules of mast cells. the most important proangiogenic molecule produced by tumor cells and by a variety of tissue (mast cells and macrophages) and peripheral blood immune cells (basophils, eosinophils, and neutrophils). the most important lymphangiogenic factors. VEGF-C is produced also by human cardiac mast cells. white adipose tissue contains several immune cells, including mast cell progenitors. membranous sac attached to the embryo. Tissue macrophages and certain mast cells originate from yolk sac progenitors.