Department of Biomedical Science and Technology, School of Biological Sciences, Ramakrishna Mission Vivekananda Educational and Research Institute (RKMVERI), 99 Sarat Bose Road, Kolkata, West Bengal, 700026, India.
Department of Cardiology, Ramakrishna Mission Seva Pratishthan Vivekananda Institute of Medical Sciences (RKMSP VIMS), 99 Sarat Bose Road, Kolkata, West Bengal, 700026, India.
Mol Biol Rep. 2024 Oct 24;51(1):1090. doi: 10.1007/s11033-024-10028-3.
Dilated cardiomyopathy (DCM) is a prevalent form of heart failure results in dilation and disruption of heart. Most strikingly a majority of the DCM cases do not have any identified etiology, hence known as idiopathic DCM (IDCM). Our study aimed to investigate the cross-talk between leukocytes and cardiomyocytes in terms of cardiac inflammation and stress response in IDCM.
60 IDCM patients and 60 age and sex matched healthy volunteers were recruited in this study based on the New York Heart Association (NYHA) guidelines. Their echocardiographic and biochemical markers were assessed and PBMCs were analyzed for leukocyte migration and inflammation. Also C2C12 myocyte cells were cultured with LPS-activated RAW264.7 monocytes to investigate the cross-talk between them.
Left ventricular (LV) dysfunction was evident in the IDCM patients which were correlated with their physical discomfort level according to NYHA classification. Their serum levels of IL-1β and TNF-α (≈ 20 pg/ml) were found to be very high along with hs-CRP and IL-2. Elevated levels of ROCK, SMA and ICAM-1 proteins indicated activation and migration of the leukocytes. During monocyte-myocyte co-culture, robust diapedesis was observed in the cultured macrophage cells towards myocytes through the transwell pores (8 µM) in presence of IL-1β and TNF-α causing ER stress and cell death in the myocytes. Inhibition of this migration or by alleviating ER stress inhibits leukocyte recruitment and ensures protection to the myocytes.
The present study showed that alleviating cellular stress and managing leukocyte migration promotes protection to the heart.
扩张型心肌病（DCM）是心力衰竭的一种常见形式，会导致心脏扩张和功能障碍。最引人注目的是，大多数 DCM 病例没有任何明确的病因，因此被称为特发性 DCM（IDCM）。我们的研究旨在探讨 IDCM 中心粒细胞与心肌细胞之间的心脏炎症和应激反应的串扰。
根据纽约心脏协会（NYHA）指南，本研究纳入了 60 名 IDCM 患者和 60 名年龄和性别匹配的健康志愿者。评估他们的超声心动图和生化标志物，并分析 PBMC 中的白细胞迁移和炎症。此外，还用 LPS 激活的 RAW264.7 单核细胞培养 C2C12 肌细胞，以研究它们之间的串扰。
IDCM 患者存在左心室（LV）功能障碍，这与他们根据 NYHA 分类的身体不适程度相关。他们的血清 IL-1β和 TNF-α（≈20pg/ml）水平非常高，同时伴有 hs-CRP 和 IL-2。ROCK、SMA 和 ICAM-1 蛋白水平升高表明白细胞的激活和迁移。在单核细胞-肌细胞共培养中，在 IL-1β和 TNF-α存在的情况下，培养的巨噬细胞细胞通过 Transwell 孔（8µM）向肌细胞发生强烈的穿胞运动，导致肌细胞内质网应激和细胞死亡。抑制这种迁移或减轻内质网应激可抑制白细胞募集并确保对肌细胞的保护。
本研究表明，减轻细胞应激和管理白细胞迁移可促进心脏保护。
