Department of Cardiology, Feicheng Mining Center Hospital, Feicheng, Shandong 271600, P.R. China.
Department of Gastroenterology, Feicheng Mining Center Hospital, Feicheng, Shandong 271600, P.R. China.
Mol Med Rep. 2021 Jul;24(1). doi: 10.3892/mmr.2021.12165. Epub 2021 May 26.
Heart failure (HF) is a progressive myocardial disease that affects pulse rate. Notably, chronic inflammation serves a crucial role in cardiac dysfunction and HF. Appropriate cardiomyocyte‑fibroblast communication is essential for cardiac function. In addition, cardiac fibroblasts (CFs) are the main cellular population in the cardiac microenvironment; therefore, determining the role of CFs in HF progression and the associated molecular basis is important. In the present study, ELISAs were performed to detect inflammatory factors in the sera of patients with HF and their association with CF activation was analyzed using Pearson's correlation coefficient. The mechanism underlying the proinflammatory phenotype of CFs was investigated via western blotting. Notably, the levels of IL10 and TNF‑α were significantly increased in the sera of patients with HF. Further analysis revealed that CFs were extensively activated in the cardiac tissues of patients with HF and released excessive amounts of cytokines, which could impair the viability of cardiomyocytes. Moreover, low‑density lipoprotein (LDL)‑induced NLRC3 inflammasome was activated in CFs, which gave rise to proinflammatory phenotypes. Targeting LDL in CFs significantly improved the functioning of cardiomyocytes and inhibited apoptosis. These findings highlighted the critical role of LDL in inflammasome activation; to the best of our knowledge, the present study is the first to reveal that CF‑induced microenvironmental inflammation may suppress cardiomyocyte viability. The present study established the cellular basis for CF activation during HF progression and provided information on the cellular interactions important for HF treatment.
心力衰竭(HF)是一种影响脉搏率的进行性心肌疾病。值得注意的是,慢性炎症在心脏功能障碍和 HF 中起着至关重要的作用。适当的心肌细胞-成纤维细胞通讯对心脏功能至关重要。此外,心脏成纤维细胞(CFs)是心脏微环境中的主要细胞群体;因此,确定 CFs 在 HF 进展中的作用及其相关的分子基础非常重要。在本研究中,通过 ELISA 检测 HF 患者血清中的炎症因子,并通过 Pearson 相关系数分析其与 CF 激活的关系。通过 Western blot 研究 CFs 促炎表型的机制。值得注意的是,HF 患者血清中的 IL10 和 TNF-α水平显著升高。进一步分析表明,HF 患者的心脏组织中 CFs 广泛激活并释放过量的细胞因子,这可能损害心肌细胞的活力。此外,低密度脂蛋白(LDL)诱导的 NLRC3 炎性小体在 CFs 中被激活,导致促炎表型。在 CFs 中靶向 LDL 可显著改善心肌细胞的功能并抑制细胞凋亡。这些发现强调了 LDL 在炎性小体激活中的关键作用;据我们所知,本研究首次揭示 CF 诱导的微环境炎症可能抑制心肌细胞活力。本研究确立了 HF 进展过程中 CF 激活的细胞基础,并提供了有关 HF 治疗重要细胞相互作用的信息。