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 language | English |
---|---|
Pages (from-to) | 1116-1123 |
Number of pages | 8 |
Journal | Arteriosclerosis, Thrombosis, and Vascular Biology |
Volume | 31 |
Issue number | 5 |
DOIs | |
Publication status | Published - May 2011 |
Keywords
- cardiac hypertrophy
- cardiac remodeling
- oxidative stress
ASJC Scopus subject areas
- Cardiology and Cardiovascular Medicine