title: Cardiomyocyte-specific expression of CYP2J2 prevents development of cardiac remodelling induced by angiotensin II.
abstract: OBJECTIVE
  Cardiac remodelling is one of the key pathological changes that occur with cardiovascular disease. Previous studies have demonstrated the beneficial effects of CYP2J2 expression on cardiac injury. In the present study, we investigated the effects of cardiomyocyte-specific CYP2J2 expression and EET treatment on angiotensin II-induced cardiac remodelling and sought to determine the underlying molecular mechanisms involved in this process.
  
  
  RESULTS
  Eight-week-old mice with cardiomyocyte-specific CYP2J2 expression (αMHC-CYP2J2-Tr) and wild-type (WT) control mice were treated with Ang-II. Ang-II treatment of WT mice induced changes in heart morphology, cardiac hypertrophy and dysfunction, as well as collagen accumulation; however, cardiomyocyte-specific expression of CYP2J2 attenuated these effects. The cardioprotective effects observed in α-MHC-CYP2J2-Tr mice were associated with peroxisome proliferator-activated receptor (PPAR)-γ activation, reduced oxidative stress, reduced NF-κB p65 nuclear translocation, and inhibition of TGF-β1/smad pathway. The effects seen with cardiomyocyte-specific expression of CYP2J2 were partially blocked by treatment with PPAR-γ antagonist GW9662. In in vitro studies, 11,12-EET(1 μmol/L) treatment attenuated cardiomyocyte hypertrophy and remodelling-related protein (collagen I, TGF-β1, TIMP1) expression by inhibiting the oxidative stress-mediated NF-κB pathway via PPAR-γ activation. Furthermore, conditioned media from neonatal cardiomyocytes treated with 11,12-EET inhibited activation of cardiac fibroblasts and TGF-β1/smad pathway.
  
  
  CONCLUSIONS
  Cardiomyocyte-specific expression of CYP2J2 or treatment with EETs protects against cardiac remodelling by attenuating oxidative stress-mediated NF-κBp65 nuclear translocation via PPAR-γ activation.
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, P. R. China.
authors.forename: Zuowen
authors.initials: Z
authors.lastname: He
authors.affiliation: Department of Physiology, Tianjin Medical University, Tianjin, P. R. China.
authors.forename: Xu
authors.initials: X
authors.lastname: Zhang
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, P. R. China.
authors.forename: Chen
authors.initials: C
authors.lastname: Chen
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, P. R. China.
authors.forename: Zheng
authors.initials: Z
authors.lastname: Wen
authors.affiliation: Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
authors.forename: Samantha L
authors.initials: SL
authors.lastname: Hoopes
authors.affiliation: Division of Intramural Research, National Institute of Environmental Health Sciences, NIH, Research Triangle Park, NC 27709, USA.
authors.forename: Darryl C
authors.initials: DC
authors.lastname: Zeldin
authors.affiliation: Department of Internal Medicine and Institute of Hypertension, Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, 1095# Jiefang Avenue, Wuhan 430030, P. R. China dwwang@tjh.tjmu.edu.cn.
authors.forename: Dao Wen
authors.initials: DW
authors.lastname: Wang
mesh_terms: D015126:8,11,14-Eicosatrienoic Acid / Q000031:analogs & derivatives / Q000494:pharmacology; D000804:Angiotensin II; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D000090762:Cytochrome P-450 CYP2J2; D003577:Cytochrome P-450 Enzyme System / Q000235:genetics / Q000378:metabolism*; D004195:Disease Models, Animal; D017379:Hypertrophy, Left Ventricular / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics / Q000503:physiopathology / Q000517:prevention & control*; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D032383:Myocytes, Cardiac / Q000187:drug effects / Q000201:enzymology* / Q000473:pathology; D018384:Oxidative Stress; D047495:PPAR gamma / Q000378:metabolism; D051381:Rats; D015398:Signal Transduction; D051996:Transcription Factor RelA / Q000378:metabolism; D016277:Ventricular Function, Left / Q000187:drug effects; D020257:Ventricular Remodeling / Q000187:drug effects
chemical_list: D047495:PPAR gamma; C498144:Rela protein, mouse; C498145:Rela protein, rat; D051996:Transcription Factor RelA; D000804:Angiotensin II; C046783:11,12-epoxy-5,8,14-eicosatrienoic acid; D003577:Cytochrome P-450 Enzyme System; D000090762:Cytochrome P-450 CYP2J2; D015126:8,11,14-Eicosatrienoic Acid
keywords: CYP2J2; Cardiac hypertrophy; Cardiac remodelling; Epoxyeicosatrienoic acids; Oxidative stress