Mast Cells and Cardiovascular Disorders

Mastocytosis is a neoplasm characterised by clonal proliferation of mast cells (MCs) in the skin and other organs, including the heart, and symptoms produced by MC-derived mediators. MC activation syndrome (MCAS) relates to increased and inappropriate activation of MCs without clonal proliferation. Mast cells are tissue-resident immune cells strategically located in different cardiac sites, e.g., myocardium, pericardium, aortic valve, and close to nerves, and in atherosclerotic plaques. The mediators (e.g., histamine, tryptase, chymase, cytokines, and chemokines) have roles in inflammation, angiogenesis, tissue remodelling, and fibrosis. They activate different cardiac resident immune cells (e.g., macrophages) and structural cells (e.g., fibroblasts and endothelial cells). MCs participate in atherosclerosis and several cardiovascular diseases (CVD), comprising allergic angina, coronary syndromes, and arrhythmias, by destabilizing and promoting atherosclerotic plaque rupture with its attendant dire consequences. Furthermore, MCs stimulate fibrosis after a myocardial infarction. MCAS is increasingly appreciated as it affects many patients previously noted to have various apparently idiopathic chronic multisystem inflammatory and/or allergic diseases or dystrophisms. Symptoms resulting from mediator release comprise flushing, hypotension, urticaria, angioedema, headache, vomiting, and diarrhea. Diagnosis is rendered by skin and/or bone marrow biopsy. Considering the increasing incidence and prevalence of MC-related diseases, guidance is needed for clinicians or researchers to select efficacious MC stabilizers that could block external stimulus signals into cells, inhibit intracellular signalling pathways, and disrupt degranulation. These novel therapies may soon find their way into the clinical arena. All relevant data and important advances in this recently recognized clinical entity are herein reviewed.