Cyclophilin A promotes cardiac hypertrophy in apolipoprotein E-deficient mice.
Cyclophilin A promotes cardiac hypertrophy in apolipoprotein E-deficient mice.
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DOI：
10.1161/atvbaha.110.214601
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发表时间：
2011-05
期刊：
影响因子：
--
通讯作者：
Berk BC
中科院分区：
文献类型：
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作者：
Satoh K;Nigro P;Zeidan A;Soe NN;Jaffré F;Oikawa M;O'Dell MR;Cui Z;Menon P;Lu Y;Mohan A;Yan C;Blaxall BC;Berk BC
亲环蛋白 A（CyPA，由 Ppia 编码）是一种促炎蛋白，针对小鼠和人类的氧化应激而分泌。我们最近证明 CyPA 增加了 Apoe−/− 小鼠主动脉中血管紧张素 II (AngII) 诱导的活性氧 (ROS) 的产生。在这项研究中，我们试图评估 CyPA 在 AngII 诱导的心脏肥大中的作用。注射 AngII（1000 ng/min/kg，持续 4 周）的 Ppia+/+ 和 Ppia−/− 小鼠之间，心脏肥大没有显着差异。因此，我们使用 Apoe−/− 小鼠研究了 CyPA 在高 ROS 和炎症条件下的作用。与 Apoe−/− 小鼠相比，Apoe−/− Ppia−/− 小鼠表现出明显较少的 AngII 诱导的心脏肥大。骨髓细胞移植表明心脏固有细胞中的CyPA在心脏肥大反应中发挥重要作用。 Apoe−/− Ppia−/− 心脏成纤维细胞中 AngII 诱导的 ROS 产生、心脏成纤维细胞增殖和迁移显着减少。此外，CyPA直接诱导培养的新生儿心肌细胞肥大。 CyPA 是 AngII 介导的心脏肥大所必需的，它可以直接增强 ROS 的产生，刺激心脏成纤维细胞的增殖和迁移，并促进心肌细胞肥大。
Cyclophilin A (CyPA, encoded by Ppia) is a pro-inflammatory protein secreted in response to oxidative stress in mice and humans. We recently demonstrated that CyPA increased angiotensin II (AngII)-induced reactive oxygen species (ROS) production in the aortas of Apoe−/− mice. In this study we sought to evaluate the role of CyPA in AngII–induced cardiac hypertrophy. Cardiac hypertrophy was not significantly different between Ppia+/+ and Ppia−/− mice infused with AngII (1000 ng/min/kg for 4 weeks). Therefore, we investigated the effect of CyPA under conditions of high ROS and inflammation using the Apoe−/− mice. In contrast to Apoe−/− mice, Apoe−/− Ppia−/− mice exhibited significantly less AngII-induced cardiac hypertrophy. Bone marrow cell transplantation showed that CyPA in cells intrinsic to the heart plays an important role in the cardiac hypertrophic response. AngII-induced ROS production, cardiac fibroblast proliferation and migration were markedly decreased in Apoe−/− Ppia−/− cardiac fibroblasts. Furthermore, CyPA directly induced the hypertrophy of cultured neonatal cardiac myocytes. CyPA is required for AngII-mediated cardiac hypertrophy by directly potentiating ROS production, stimulating the proliferation and migration of cardiac fibroblasts, and promoting cardiac myocyte hypertrophy.