Diny Nicola Laura, Wood Megan Kay, Won Taejoon, Talor Monica Vladut, Lukban Clarisse, Bedja Djahida, Wang Nadan, Kalinoski Hannah, Daoud Abdel, Talbot C Conover, Leei Lin Brian, Čiháková Daniela
W. Harry Feinstone Department of Molecular Microbiology and Immunology, Johns Hopkins University Bloomberg School of Public Health, Baltimore, MD 21205, USA.
Department of Pathology, Johns Hopkins University School of Medicine, Baltimore, MD 21205, USA.
iScience. 2023 Sep 21;26(10):107990. doi: 10.1016/j.isci.2023.107990. eCollection 2023 Oct 20.
Hypereosinophilic syndrome is a progressive disease with extensive eosinophilia that results in organ damage. Cardiac pathologies are the main reason for its high mortality rate. A better understanding of the mechanisms of eosinophil-mediated tissue damage would benefit therapeutic development. Here, we describe the cardiac pathologies that developed in a mouse model of hypereosinophilic syndrome. These IL-5 transgenic mice exhibited decreased left ventricular function at a young age which worsened with age. Mechanistically, we demonstrated infiltration of activated eosinophils into the heart tissue that led to an inflammatory environment. Gene expression signatures showed tissue damage as well as repair and remodeling processes. Cardiomyocytes from IL-5Tg mice exhibited significantly reduced contractility relative to wild type (WT) controls. This impairment may result from the inflammatory stress experienced by the cardiomyocytes and suggest that dysregulation of contractility and Ca reuptake in cardiomyocytes contributes to cardiac dysfunction at the whole organ level in hypereosinophilic mice.
高嗜酸性粒细胞综合征是一种进展性疾病，伴有广泛的嗜酸性粒细胞增多，可导致器官损伤。心脏病变是其高死亡率的主要原因。更好地了解嗜酸性粒细胞介导的组织损伤机制将有助于治疗方法的开发。在此，我们描述了高嗜酸性粒细胞综合征小鼠模型中出现的心脏病变。这些白细胞介素-5转基因小鼠在年轻时左心室功能就已下降，且随年龄增长而恶化。从机制上讲，我们证明了活化的嗜酸性粒细胞浸润到心脏组织中，导致了炎症环境。基因表达特征显示了组织损伤以及修复和重塑过程。与野生型（WT）对照相比，白细胞介素-5转基因小鼠的心肌细胞收缩力显著降低。这种损伤可能是由心肌细胞所经历的炎症应激导致的，这表明心肌细胞收缩性和钙再摄取的失调导致了高嗜酸性粒细胞小鼠整个器官水平的心脏功能障碍。
