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Abstract：
The role of the mitochondrial calcium uniporter (MCU) in energy dysfunction and hypertrophy in heart failure (HF) remains unknown. In angiotensin II (ANGII)-induced hypertrophic cardiac cells we have shown that hypertrophic cells overexpress MCU and present bioenergetic dysfunction. However, by silencing MCU, cell hypertrophy and mitochondrial dysfunction are prevented by blocking mitochondrial calcium overload, increase mitochondrial reactive oxygen species, and activation of nuclear factor kappa B-dependent hypertrophic and proinflammatory signaling. Moreover, we identified a calcium/calmodulin-independent protein kinase II/cyclic adenosine monophosphate response element-binding protein signaling modulating MCU upregulation by ANGII. Additionally, we found upregulation of MCU in ANGII-induced left ventricular HF in mice, and in the LV of HF patients, which was correlated with pathological remodeling. Following left ventricular assist device implantation, MCU expression decreased, suggesting tissue plasticity to modulate MCU expression.
摘要：
线粒体钙离子转运蛋白（MCU）在心力衰竭（HF）的能量功能障碍和肥大中的作用仍然未知。在血管紧张素II（ANGII）诱导的肥大心肌细胞中，我们已经表明肥大细胞过表达MCU并表现出生物能功能障碍。然而,通过沉默MCU，通过阻断线粒体钙超载来预防细胞肥大和线粒体功能障碍，增加线粒体活性氧，和核因子κB依赖性肥大和促炎信号的激活。此外，我们确定了一种钙/钙调蛋白非依赖性蛋白激酶II/环磷酸腺苷反应元件结合蛋白信号调节ANGII上调MCU。此外,我们发现MCU在ANGII诱导的小鼠左心室HF中上调，在HF患者的LV中，与病理性重塑有关。左心室辅助装置植入后,MCU表达式下降，提示组织可塑性调节MCU表达。
