title: Phosphoinositide 3-kinase inhibitor LY294002 ameliorates the severity of myosin-induced myocarditis in mice.
abstract: Myocarditis, characterized by myocyte necrosis, fibrosis, and degeneration with mononuclear cell infiltration, always causes heart failure in patients. Phosphoinositide 3-kinase (PI3K) is a pivotal kinase known to regulate inflammatory responses in cardiac diseases. Although previous research has suggested that PI3K was involved in cardiac diseases such as myocardial infarction, it is still unclear whether the inhibition of PI3K is essential for the treatment of myosin-induced myocarditis. The aim of this study was to explore whether pharmacological blockade of PI3K is able to protect mice against experimental autoimmune myocarditis (EAM).
  
  
  
  We used the cardiac myosin-induced murine EAM model to investigate the therapeutic effect of PI3K inhibitor LY294002 on autoimmune myocarditis in mice.
  
  
  
  LY294002 significantly alleviated EAM injury in mice, as indicated by the reduction of cardiac necrosis, inflammatory infiltrates, and CD3(+) T cells. LY294002 also decreased the expression of p-Akt upon cardiac myosin treatment in the cardiac tissue of the mice. In the present study, LY294002 resulted in a moderate reduction in absolute CD4(+) cell numbers and a significant decrease in the absolute numbers of CD8(+) cells. Consequently, LY294002 increased the CD4(+)/CD8(+) ratio compared with peptide treatment alone.
  
  
  
  This report provides evidence that PI3K inhibitor LY294002 has potent effects against cardiac injury caused by EAM, suggesting that it has therapeutic value for the treatment of myocarditis.
authors.affiliation: Department of cardiovascular surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China; Department of cardiothoracic surgery, Taihe Hospital affilated to Hubei university of medicine, Shiyan 442000, Hubei, P.R. China.
authors.forename: H S
authors.initials: HS
authors.lastname: Liu
authors.affiliation: Department of cardiothoracic surgery, Taihe Hospital affilated to Hubei university of medicine, Shiyan 442000, Hubei, P.R. China.
authors.forename: J
authors.initials: J
authors.lastname: Zhang
authors.affiliation: Department of cardiothoracic surgery, Taihe Hospital affilated to Hubei university of medicine, Shiyan 442000, Hubei, P.R. China.
authors.forename: J-L
authors.initials: JL
authors.lastname: Guo
authors.affiliation: Department of cardiothoracic surgery, Taihe Hospital affilated to Hubei university of medicine, Shiyan 442000, Hubei, P.R. China.
authors.forename: C Y
authors.initials: CY
authors.lastname: Lin
authors.affiliation: Department of cardiovascular surgery, Renmin Hospital of Wuhan University, Wuhan 430060, Hubei, P.R. China. Electronic address: wangzhiwei@whu.edu.cn.com.
authors.forename: Z-W
authors.initials: ZW
authors.lastname: Wang
mesh_terms: D000818:Animals; D001327:Autoimmune Diseases / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D002867:Chromones / Q000494:pharmacology / Q000627:therapeutic use*; D016207:Cytokines / Q000097:blood; D004353:Drug Evaluation, Preclinical; D005260:Female; D007114:Immunization; D051379:Mice; D008807:Mice, Inbred BALB C; D009025:Morpholines / Q000494:pharmacology / Q000627:therapeutic use*; D009205:Myocarditis / Q000188:drug therapy* / Q000201:enzymology / Q000209:etiology / Q000473:pathology; D009206:Myocardium / Q000276:immunology / Q000473:pathology; D018995:Myosin Heavy Chains / Q000276:immunology / Q000633:toxicity; D010446:Peptide Fragments / Q000276:immunology / Q000633:toxicity; D000081082:Phosphoinositide-3 Kinase Inhibitors; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D051057:Proto-Oncogene Proteins c-akt / Q000378:metabolism; D024723:Ventricular Myosins / Q000276:immunology / Q000633:toxicity
chemical_list: D002867:Chromones; D016207:Cytokines; D009025:Morpholines; D010446:Peptide Fragments; D000081082:Phosphoinositide-3 Kinase Inhibitors; C085911:2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one; D051057:Proto-Oncogene Proteins c-akt; D024723:Ventricular Myosins; D018995:Myosin Heavy Chains
keywords: LY294002; Myosin-induced myocarditis; PI3K