Cyclophilin A promotes cardiac hypertrophy in apolipoprotein E-deficient mice.

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.

CONCLUSIONS:

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.

• Authors: 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
• Journal: Arteriosclerosis, thrombosis, and vascular biology (Arterioscler Thromb Vasc Biol) Vol. 31 Issue 5 Pg. 1116-23 (May 2011) ISSN: 1524-4636 [Electronic] United States
• PMID: 21330604 (Publication Type: Journal Article, Research Support, N.I.H., Extramural, Research Support, Non-U.S. Gov't)

Chemical References

• Apolipoproteins E
• Reactive Oxygen Species
• Recombinant Proteins
• Angiotensin II
• Cyclophilin A

Topics

• Angiotensin II
• Animals
• Animals, Newborn
• Apolipoproteins E (deficiency, genetics)
• Bone Marrow Cells (metabolism)
• Bone Marrow Transplantation
• Cardiomegaly (chemically induced, enzymology, genetics, immunology, pathology, prevention & control)
• Cell Communication
• Cell Movement
• Cell Proliferation
• Cells, Cultured
• Cyclophilin A (deficiency, genetics, metabolism)
• Disease Models, Animal
• Fibroblasts (metabolism)
• Inflammation (immunology, metabolism)
• Male
• Mice
• Mice, Inbred C57BL
• Mice, Knockout
• Myocardium (enzymology, immunology, pathology)
• Myocytes, Cardiac (metabolism)
• Oxidative Stress
• Rats
• Rats, Sprague-Dawley
• Reactive Oxygen Species (metabolism)
• Recombinant Proteins (metabolism)
• Time Factors