Cyclophilin a promotes cardiac hypertrophy in apolipoprotein e-deficient mice

Kimio Satoh, Patrizia Nigro, Asad Zeidan, Nwe Nwe Soe, Fabrice Jaffré, Masayoshi Oikawa, Michael R. O'Dell, Zhaoqiang Cui, Prashanthi Menon, Yan Lu, Amy Mohan, Chen Yan, Burns C. Blaxall, Bradford C. Berk

Research output: Contribution to journalArticlepeer-review

Abstract

Objective- Cyclophilin A (CyPA, encoded by Ppia) is a proinflammatory protein secreted in response to oxidative stress in mice and humans. We recently demonstrated that CyPA increased angiotensin II (Ang II)-induced reactive oxygen species (ROS) production in the aortas of apolipoprotein E (apoE -/-) mice. In this study, we sought to evaluate the role of CyPA in Ang II-induced cardiac hypertrophy. Methods and Results- Cardiac hypertrophy was not significantly different between Ppia+/+ and Ppia-/- mice infused with Ang II (1000 ng/min per 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 Ang II-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. Ang II-induced ROS production, cardiac fibroblast proliferation, and cardiac fibroblast migration were markedly decreased in apoE-/-Ppia cardiac fibroblasts. Furthermore, CyPA directly induced the hypertrophy of cultured neonatal cardiac myocytes. Conclusion- CyPA is required for Ang II-mediated cardiac hypertrophy by directly potentiating ROS production, stimulating the proliferation and migration of cardiac fibroblasts, and promoting cardiac myocyte hypertrophy.

Original languageEnglish
Pages (from-to)1116-1123
Number of pages8
JournalArteriosclerosis, Thrombosis, and Vascular Biology
Volume31
Issue number5
DOIs
Publication statusPublished - May 2011

Keywords

  • cardiac hypertrophy
  • cardiac remodeling
  • oxidative stress

ASJC Scopus subject areas

  • Cardiology and Cardiovascular Medicine

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