Cardiovascular disease is one of the leading causes of death worldwide and has a high prevalence. Insulin‐like growth factor‐II receptor α (IGF‐IIRα) acts as a stress‐inducible negative regulator. This study focused on the substantial impact of heightened expression of IGF‐IIRα in cardiac myoblasts and its association with the exacerbation of cardiac dysfunction. Using lipopolysaccharide (LPS)‐induced H9c2 cardiac myoblasts as a model for sepsis, we aimed to elucidate the molecular interactions between IGF‐IIRα and LPS in exacerbating cardiac injury. Our findings demonstrated a synergistic induction of cardiac inflammation and hypertrophy by LPS stimulation and IGF‐IIRα overexpression, leading to decreased cell survival. Excessive calcineurin activity, triggered by this combined condition, was identified as a key factor exacerbating the negative effects on cell survival. Cellular changes such as cell enlargement, disrupted actin filaments, and upregulation of hypertrophy‐related and inflammation‐related proteins contributed to the overall hypertrophic and inflammatory responses. Overexpression of IGF‐IIRα also exacerbated apoptosis induced by LPS in H9c2 cardiac myoblasts. Inhibiting calcineurin in LPS‐treated H9c2 cardiac myoblasts with IGF‐IIRα overexpression effectively reversed the detrimental effects, reducing cell damage and mitigating apoptosis‐related cardiac mechanisms. Our study suggests that under sepsis‐like conditions in the heart with IGF‐IIRα overexpression, hyperactivation of calcineurin worsens cardiac damage. Suppressing IGF‐IIRα and calcineurin expression could be a potential intervention to alleviate the impact of the illness and improve cardiac function.

中文翻译：

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增强的 IGF-IIRα 表达通过钙调磷酸酶激活加剧脂多糖诱导的心脏炎症、肥大和细胞凋亡


心血管疾病是全球主要死亡原因之一，患病率很高。胰岛素样生长因子 II 受体α （IGF-IIRα） 充当应激诱导的负调节因子。本研究的重点是 IGF-IIRα 在心脏成肌细胞中表达升高的重大影响及其与心功能不全恶化的相关性。使用脂多糖 （LPS） 诱导的 H9c2 心脏成肌细胞作为脓毒症模型，我们旨在阐明 IGF-IIRα 和 LPS 之间在加剧心脏损伤中的分子相互作用。我们的研究结果表明，LPS 刺激和 IGF-IIRα 过表达协同诱导心脏炎症和肥大，导致细胞存活率降低。由这种综合条件触发的过高钙调磷酸酶活性被确定为加剧对细胞存活的负面影响的关键因素。细胞变化，例如细胞增大、肌动蛋白丝断裂以及肥大相关和炎症相关蛋白的上调，导致整体肥大和炎症反应。IGF-IIRα 的过表达也加剧了 LPS 在 H9c2 心脏成肌细胞中诱导的细胞凋亡。在 LPS 处理的 IGF-IIRα 过表达的 H9c2 心脏成肌细胞中抑制钙调磷酸酶可有效逆转有害影响，减少细胞损伤并减轻细胞凋亡相关的心脏机制。我们的研究表明，在 IGF-IIRα 过表达的心脏脓毒症样情况下，钙调磷酸酶的过度激活会加重心脏损伤。抑制 IGF-IIRα 和钙调磷酸酶表达可能是减轻疾病影响和改善心脏功能的潜在干预措施。