CYP epoxygenase 2J2 prevents cardiac fibrosis by suppression of transmission of pro-inflammation from cardiomyocytes to macrophages.

Abstract

Cytochrome P450 epoxygenase (CYP450)-derived epoxyeicosatrienoic acids (EETs) are important regulators of cardiac remodeling; but the underlying mechanism remains unclear. The present study aimed to elucidate how EETs regulated cardiac fibrosis in response to isoprenaline (Iso) or angiotensin (Ang) II. Cardiac-specific human CYP2J2 transgenic mice (Tr) and wild-type (WT) C57BL/6 littermates were infused with Iso- or Ang II. Two weeks after infusion, Tr mice showed more alleviative cardiac fibrosis and inflammation compared with WT mice. In vitro, we found Iso or Ang II induced nuclear transfer of NF-κB p65 and inflammatory cytokines expression in cardiomyocytes. Furthermore, inflammation response emerged in macrophages cultured in cardiomyocytes-conditioned medium. When pretreatment with 14,15-EET in cardiomyocytes, the inflammatory response was markedly suppressed and the transmission of inflammation from cardiomyocytes to macrophages was reduced. In conclusion, CYP2J2 and EETs prevent cardiac fibrosis and cardiac dysfunction by suppressing transmission of pro-inflammation from cardiomyocytes to macrophages in heart, suggesting that elevation of EETs level could be a potential strategy to prevent cardiac fibrosis.

• Authors: Lei Yang, Li Ni, Quanlu Duan, Xingxu Wang, Chen Chen, Song Chen, Sandip Chaugai, D C Zeldin, Jia Rong Tang, Dao Wen Wang
• Journal: Prostaglandins & other lipid mediators (Prostaglandins Other Lipid Mediat) 2015 Jan-Mar Vol. 116-117 Pg. 64-75 ISSN: 1098-8823 [Print] United States
• PMID: 25686540 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: Copyright © 2015 Elsevier Inc. All rights reserved.

Chemical References

• CYP2J2 protein, human
• Rela protein, mouse
• Transcription Factor RelA
• 14,15-epoxy-5,8,11-eicosatrienoic acid
• Cytochrome P-450 Enzyme System
• Cytochrome P-450 CYP2J2
• 8,11,14-Eicosatrienoic Acid

Topics

• 8,11,14-Eicosatrienoic Acid (analogs & derivatives, genetics, metabolism)
• Animals
• Cytochrome P-450 CYP2J2
• Cytochrome P-450 Enzyme System (genetics, metabolism)
• Endomyocardial Fibrosis (enzymology, genetics, pathology)
• Humans
• Inflammation (genetics, metabolism, pathology)
• Macrophages (enzymology, pathology)
• Mice
• Mice, Transgenic
• Myocytes, Cardiac (enzymology, pathology)
• Transcription Factor RelA (genetics, metabolism)