Mast cells are tissue-resident immune cells strategically located in different compartments of the normal human heart (the myocardium, pericardium, aortic valve and close to nerves) as well as in atherosclerotic plaques. Cardiac mast cells produce a broad spectrum of vasoactive and proinflammatory mediators, which have potential roles in inflammation, angiogenesis, lymphangiogenesis, tissue remodeling and fibrosis. Mast cells release preformed mediators (e.g., histamine, tryptase, chymase) and de novo synthesized mediators [e.g., cysteinyl leukotriene C4 (LTC4) and prostaglandin D2 (PGD2)], as well as cytokines and chemokines, which can activate different resident immune cells (e.g., macrophages) and structural cells (e.g., fibroblasts, endothelial cells) in the human heart and aorta. The transcriptional profiles of various mast cell populations highlight their potential heterogeneity and distinct gene and proteome expression. Mast cell plasticity and/or heterogeneity enable these cells the potential for performing different, even opposite, functions in response to changing tissue contexts. Human cardiac mast cells display significant differences compared to mast cells isolated from other organs. These characteristics make cardiac mast cells intriguing, given their dichotomous potential roles of inducing or protecting against cardiovascular diseases. Identification of cardiac mast cell subpopulations represents a prerequisite for understanding their potential multifaceted roles in health and disease. Several new drugs specifically targeting human mast cell activation are under development or in clinical trials. Mast cells and/or their subpopulations can potentially represent novel therapeutic targets for cardiovascular disorders.

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肥大细胞：心血管疾病的新治疗途径？

肥大细胞是组织驻留的免疫细胞，战略性地位于正常人心脏的不同室（心肌、心包、主动脉瓣和靠近神经）以及动脉粥样硬化斑块中。心脏肥大细胞产生广泛的血管活性和促炎介质，这些介质在炎症、血管生成、淋巴管生成、组织重塑和纤维化中具有潜在作用。肥大细胞释放预先形成的介质（例如组胺、类胰蛋白酶、糜酶）和从头合成的介质[例如半胱氨酰白三烯C4（LTC4）和前列腺素D2（PGD2）]以及细胞因子和趋化因子，它们可以激活不同的驻留免疫细胞人类心脏和主动脉中的细胞（例如巨噬细胞）和结构细胞（例如成纤维细胞、内皮细胞）。各种肥大细胞群的转录谱突出了它们潜在的异质性以及独特的基因和蛋白质组表达。肥大细胞的可塑性和/或异质性使这些细胞能够响应组织环境的变化而执行不同的甚至相反的功能。与从其他器官分离的肥大细胞相比，人类心脏肥大细胞表现出显着差异。鉴于心脏肥大细胞在诱导或预防心血管疾病方面具有二分的潜在作用，这些特征使心脏肥大细胞变得有趣。心脏肥大细胞亚群的鉴定是了解其在健康和疾病中潜在的多方面作用的先决条件。几种专门针对人类肥大细胞激活的新药正在开发或进行临床试验。肥大细胞和/或其亚群可能代表心血管疾病的新治疗靶点。