Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212000, China.
Department of Cardiology, Affiliated Hospital of Jiangsu University, Zhenjiang, Jiangsu, 212000, China.
Mol Cell Endocrinol. 2020 Dec 1;518:110990. doi: 10.1016/j.mce.2020.110990. Epub 2020 Aug 14.
Excessive reactive oxygen species (ROS) are a critical driver of cardiac hypertrophy developing into heart failure. Cyclophilin A (CyPA), a member of the cyclophilin family, has been highlighted as a main secreted ROS-induced factor. The mechanism by which extracellular CyPA interacts with cardiomyocytes is unclear. We showed that extracellular CyPA is upregulated in cardiac hypertrophy rats and expressed around hypertrophic cardiomyocytes. Cell experiments further confirmed that extracellular CyPA induces H9c2 cardiomyocytes hypertrophy via ROS generation. Extracellular CyPA-induced ROS is derived from nicotinamide-adenine dinucleotide phosphate (NADPH) oxidase, and extracellular CyPA activates p47phox membrane translocation through ERK1/2 pathway. When blocking extracellular matrix metalloproteinase inducer (EMMPRIN), most of the extracellular CyPA effects were significantly inhibited. The current study shows that extracellular CyPA is one of the key factors linking oxidative stress and cardiac hypertrophy, and may be a potential target for cardiac hypertrophy therapy.
过量的活性氧（ROS）是导致心肌肥厚发展为心力衰竭的关键因素。亲环素 A（CyPA）作为细胞色素家族的一员，已被确定为主要的分泌 ROS 诱导因子。细胞外 CyPA 与心肌细胞相互作用的机制尚不清楚。我们发现，细胞外 CyPA 在心肌肥厚大鼠中上调，并在肥大心肌细胞周围表达。细胞实验进一步证实，细胞外 CyPA 通过产生 ROS 诱导 H9c2 心肌细胞肥大。细胞外 CyPA 诱导的 ROS 来源于烟酰胺腺嘌呤二核苷酸磷酸（NADPH）氧化酶，细胞外 CyPA 通过 ERK1/2 途径激活 p47phox 膜易位。当阻断细胞外基质金属蛋白酶诱导因子（EMMPRIN）时，大部分细胞外 CyPA 的作用明显受到抑制。本研究表明，细胞外 CyPA 是连接氧化应激和心肌肥厚的关键因素之一，可能是心肌肥厚治疗的潜在靶点。
