title: Valsartan Attenuates KIR2.1 by Downregulating the Th1 Immune Response in Rats Following Myocardial Infarction.
abstract: BACKGROUND
  Myocardial infarction (MI) results in decreased inward-rectifier K⁺ current (IK1), which is mediated primarily by the Kir2.1 protein and is accompanied by upregulated T cells. Interferon γ (IFN-γ), secreted predominantly by Th1 cells, causes a decrease in IK1 in microglia. Whether Th1 cells can induce IK1/Kir2.1 remodeling following MI and whether valsartan can ameliorate this phenomenon remain unclear.
  
  
  METHODS
  Rats experiencing MI received either valsartan or saline for 7 days. Th1-enriched lymphocytes and myocytes were cocultured with or without valsartan treatment. Th1 cells were monitored by flow cytometry. The protein levels of Kir2.1 were detected by Western blot analyses. IK1 was recorded through whole-cell patch clamping. The plasma levels of IFN-γ, interleukin 2, and tumor necrosis factor α were detected by enzyme-linked immunosorbent assay.
  
  
  RESULTS
  Th1 cell number and cytokine expression levels were higher following MI, and the Kir2.1 protein level was decreased. In MI rats, valsartan reduced Th1 cell number and cytokine expression levels and increased the Kir2.1 expression and the IK1 current compared with the rats that received saline treatment; these results are consistent with the effect of valsartan in cocultured lymphocytes and myocytes. In vitro, IFN-γ overexpression suppressed the IK1 current, whereas interleukin 2 and tumor necrosis factor α had no significant effect on the current, establishing that Th1 cell regulation of IK1/Kir2.1 expression is mainly dependent on IFN-γ.
  
  
  CONCLUSIONS
  Valsartan ameliorates IK1/Kir2.1 remodeling by downregulating the Th1 immune response following MI.
authors.affiliation: *Shandong University, School of Medicine, Ji'nan, Shandong, China; and†Department of Cardiology, Qianfoshan Hospital of Shandong Province, Ji'nan, Shandong, China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Li
authors.forename: Hesheng
authors.initials: H
authors.lastname: Hu
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.forename: Mei
authors.initials: M
authors.lastname: Xue
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Li
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Cheng
authors.forename: Yongli
authors.initials: Y
authors.lastname: Xuan
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.forename: Suhua
authors.initials: S
authors.lastname: Yan
mesh_terms: D047228:Angiotensin II Type 1 Receptor Blockers / Q000494:pharmacology*; D000818:Animals; D002478:Cells, Cultured; D018920:Coculture Techniques; D004195:Disease Models, Animal; D015536:Down-Regulation; D006439:Hemodynamics / Q000187:drug effects; D007371:Interferon-gamma / Q000097:blood; D007376:Interleukin-2 / Q000097:blood; D008297:Male; D008564:Membrane Potentials; D009203:Myocardial Infarction / Q000097:blood / Q000188:drug therapy* / Q000276:immunology / Q000503:physiopathology; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000378:metabolism; D011188:Potassium / Q000378:metabolism; D024661:Potassium Channels, Inwardly Rectifying / Q000187:drug effects* / Q000378:metabolism; D017208:Rats, Wistar; D018417:Th1 Cells / Q000187:drug effects* / Q000276:immunology / Q000378:metabolism; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood; D000068756:Valsartan / Q000494:pharmacology*
chemical_list: D047228:Angiotensin II Type 1 Receptor Blockers; D007376:Interleukin-2; C575188:KCNJ2 protein, rat; D024661:Potassium Channels, Inwardly Rectifying; D014409:Tumor Necrosis Factor-alpha; D000068756:Valsartan; D007371:Interferon-gamma; D011188:Potassium