title: Targeting androgen receptor with ASC-J9 attenuates cardiac injury and dysfunction in experimental autoimmune myocarditis by reducing M1-like macrophage.
abstract: Macrophages are important mediators in inflammatory cardiovascular diseases. Experimental autoimmune myocarditis (EAM) is characterized by pronounced macrophages infiltration, cardiac necrosis and cardiac fibrosis. Androgen receptor (AR) is a regulator of immune system which can control macrophages' infiltration and function in various inflammatory-related diseases. However, the effect of AR on the inflammatory response in EAM is unknown. Our study aims to investigate the potential role of AR on the development of autoimmune myocarditis.
  
  
  
  In our study, we found that AR was increased in the myocardium and was associated with the time-course of EAM progression, which motivated us to use ASC-J9 (an enhancer of AR degradation). The results revealed that ASC-J9 administration in EAM mice resulted in an attenuation in the severity of disease and cardiac injury, a reduced CD4+T cell response, reduced monocyte/macrophage infiltration, and decreases in the pro-inflammatory cytokines. Furthermore, ASC-J9 was also found to prevent Raw264.7 cells polarization to M1 macrophages in response to LPS by upregulating suppressor of cytokine signaling 1(SOCS1) and downregulating signal transducer and activator of the transcription 5(STAT5) activity.
  
  
  
  AR facilitated EAM development, and targeting AR with ASC-J9 attenuated cardiac injury and dysfunction by inhibiting macrophages polarization towards M1 macrophages.
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Wenhan
authors.initials: W
authors.lastname: Ma
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Ya
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Shuai
authors.initials: S
authors.lastname: Lu
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: LianHua
authors.initials: L
authors.lastname: Yan
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China.
authors.forename: Fen
authors.initials: F
authors.lastname: Hu
authors.affiliation: Laboratory of Cardiovascular Immunology, Institute of Cardiology, Union Hospital, Tongji Medical College of Huazhong University of Science and Technology, Wuhan, China. Electronic address: wuxiaohongtian@163.com.
authors.forename: ZhaoHui
authors.initials: Z
authors.lastname: Wang
mesh_terms: D059002:Androgen Receptor Antagonists / Q000494:pharmacology*; D000818:Animals; D001327:Autoimmune Diseases / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D015153:Blotting, Western; D002460:Cell Line; D003474:Curcumin / Q000031:analogs & derivatives / Q000494:pharmacology; D006335:Heart Injuries / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D008070:Lipopolysaccharides / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism; D008807:Mice, Inbred BALB C; D009000:Monocytes / Q000187:drug effects / Q000378:metabolism; D009205:Myocarditis / Q000378:metabolism / Q000503:physiopathology / Q000517:prevention & control*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D011944:Receptors, Androgen / Q000378:metabolism*; D020133:Reverse Transcriptase Polymerase Chain Reaction; D050799:STAT5 Transcription Factor / Q000378:metabolism; D015398:Signal Transduction / Q000187:drug effects; D000071222:Suppressor of Cytokine Signaling 1 Protein / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000235:genetics / Q000378:metabolism
chemical_list: D059002:Androgen Receptor Antagonists; D003474:Curcumin; D008070:Lipopolysaccharides; D011944:Receptors, Androgen; D050799:STAT5 Transcription Factor; D000071222:Suppressor of Cytokine Signaling 1 Protein; D014409:Tumor Necrosis Factor-alpha; C471106:ASC-J9 compound; C491590:Socs1 protein, mouse
keywords: Androgen receptor; Experimental autoimmune myocarditis; Macrophage; SOCS1; STAT5