Department of Translational Medical Sciences, University of Naples Federico II, Via S. Pansini 5, Naples 80131, Italy.
World Allergy Organization (WAO), Center of Excellence (CoE), Via S. Pansini 5, Naples 80131, Italy.
Cardiovasc Res. 2024 May 29;120(7):681-698. doi: 10.1093/cvr/cvae066.
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 remodelling, and fibrosis. Mast cells release preformed mediators (e.g. histamine, tryptase, and chymase) and de novo synthesized mediators (e.g. cysteinyl leukotriene C4 and prostaglandin D2), as well as cytokines and chemokines, which can activate different resident immune cells (e.g. macrophages) and structural cells (e.g. fibroblasts and 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 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 with 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.
肥大细胞是组织驻留的免疫细胞，战略性地位于正常人心（心肌、心包、主动脉瓣和靠近神经）以及动脉粥样硬化斑块的不同部位。心肌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（如组胺、胰蛋白酶和糜蛋白酶）和新合成的介质（如半胱氨酰白三烯 C4 和前列腺素 D2），以及细胞因子和趋化因子，这些物质可以激活人心和主动脉中的不同常驻免疫细胞（如巨噬细胞）和结构细胞（如成纤维细胞和内皮细胞）。各种肥大细胞群体的转录谱突出了它们的潜在异质性和独特的基因和蛋白质组表达。肥大细胞的可塑性和异质性使这些细胞能够根据组织环境的变化发挥不同的、甚至相反的功能。与人心脏肥大细胞与其他器官分离的肥大细胞相比，具有显著差异。这些特征使心脏肥大细胞具有吸引力，因为它们具有诱导或预防心血管疾病的双重潜在作用。鉴定心脏肥大细胞亚群是理解它们在健康和疾病中潜在多方面作用的前提。几种专门针对人类肥大细胞激活的新药正在开发或临床试验中。肥大细胞及其亚群可能代表心血管疾病的新治疗靶点。
