title: 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.
  
  
  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.affiliation: Aab Cardiovascular Research Institute, Department of Medicine, University of Rochester School of Medicine and Dentistry, Box CVRI, 601 Elmwood Ave, Rochester, NY 14642, USA.
authors.forename: Kimio
authors.initials: K
authors.lastname: Satoh
authors.forename: Patrizia
authors.initials: P
authors.lastname: Nigro
authors.forename: Asad
authors.initials: A
authors.lastname: Zeidan
authors.forename: Nwe Nwe
authors.initials: NN
authors.lastname: Soe
authors.forename: Fabrice
authors.initials: F
authors.lastname: Jaffré
authors.forename: Masayoshi
authors.initials: M
authors.lastname: Oikawa
authors.forename: Michael R
authors.initials: MR
authors.lastname: O'Dell
authors.forename: Zhaoqiang
authors.initials: Z
authors.lastname: Cui
authors.forename: Prashanthi
authors.initials: P
authors.lastname: Menon
authors.forename: Yan
authors.initials: Y
authors.lastname: Lu
authors.forename: Amy
authors.initials: A
authors.lastname: Mohan
authors.forename: Chen
authors.initials: C
authors.lastname: Yan
authors.forename: Burns C
authors.initials: BC
authors.lastname: Blaxall
authors.forename: Bradford C
authors.initials: BC
authors.lastname: Berk
mesh_terms: D000804:Angiotensin II; D000818:Animals; D000831:Animals, Newborn; D001057:Apolipoproteins E / Q000172:deficiency* / Q000235:genetics; D001854:Bone Marrow Cells / Q000378:metabolism; D016026:Bone Marrow Transplantation; D006332:Cardiomegaly / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics / Q000276:immunology / Q000473:pathology / Q000517:prevention & control; D002450:Cell Communication; D002465:Cell Movement; D049109:Cell Proliferation; D002478:Cells, Cultured; D021984:Cyclophilin A / Q000172:deficiency / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D005347:Fibroblasts / Q000378:metabolism; D007249:Inflammation / Q000276:immunology / Q000378:metabolism; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009206:Myocardium / Q000201:enzymology* / Q000276:immunology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism; D018384:Oxidative Stress; D051381:Rats; D017207:Rats, Sprague-Dawley; D017382:Reactive Oxygen Species / Q000378:metabolism; D011994:Recombinant Proteins / Q000378:metabolism; D013997:Time Factors
chemical_list: D001057:Apolipoproteins E; D017382:Reactive Oxygen Species; D011994:Recombinant Proteins; D000804:Angiotensin II; D021984:Cyclophilin A