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）是导致心脏肥大发展为心力衰竭的关键驱动因素。亲环蛋白家族的成员亲环蛋白A（CyPA）已被强调为ROS诱导的主要分泌因子。细胞外CyPA与心肌细胞相互作用的机制尚不清楚。我们表明，细胞外CyPA在心脏肥大大鼠中上调，并在肥厚型心肌细胞周围表达。细胞实验进一步证实，细胞外CyPA通过ROS产生诱导H9c2心肌肥大。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。阻断细胞外基质金属蛋白酶诱导剂（EMMPRIN）时，大多数细胞外CyPA的作用被显着抑制。当前的研究表明，细胞外CyPA是连接氧化应激和心脏肥大的关键因素之一，并且可能成为心脏肥大治疗的潜在靶标。