title: Valsartan ameliorates KIR2.1 in rats with myocardial infarction via the NF-κB-miR-16 pathway.
abstract: BACKGROUND
  MicroRNAs have an important role in regulating arrhythmogenesis. MicroRNA-16 (miR-16) is predicted to target KCNJ2. The regulation of miR-16 is primarily due to NF-κB. Whether valsartan could downregulate miR-16 via the inhibition of NF-κB after MI and whether miR-16 targets KCNJ2 remain unclear.
  
  
  METHODS
  MI rats received valsartan or saline for 7days. The protein levels of NF-κB p65, inhibitor κBα (IκBα), and Kir2.1 were detected by Western blot analysis. The mRNA levels of Kir2.1 and miR-16 were examined by quantitative real-time PCR. Whole cell patch-clamp techniques were applied to record IK1.
  
  
  RESULTS
  MiR-16 expression was higher in the infarct border, and was accompanied by a depressed IK1/KIR2.1 level. Additionally, miR-16 overexpression suppressed KCNJ2/KIR2.1 expression. In contrast, miR-16 inhibition or binding-site mutation enhanced KCNJ2/KIR2.1 expression, establishing KCNJ2 as a miR-16 target. In the MI rats, compared to saline treatment, valsartan reduced NF-κB p65 and miR-16 expression and increased IκBα and Kir2.1 expression. In vitro, angiotensin II increased miR-16 expression and valsartan inhibited it. Overexpressing miR-16 in cells treated with valsartan abrogated its beneficial effect on KCNJ2/Kir2.1. NF-κB activation directly upregulates miR-16 expression.
  
  
  CONCLUSIONS
  miR-16 controls KCNJ2 expression, and valsartan ameliorates Kir2.1 after MI partly depending on the NF-κB-miR-16 pathway.
authors.affiliation: School of Medicine, Shandong University, Ji'nan, Shandong, China.
authors.forename: Xinran
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Qianfoshan Hospital of Shandong Province, Ji'nan, Shandong, China.
authors.forename: Hesheng
authors.initials: H
authors.lastname: Hu
authors.affiliation: Department of Cardiology, Qianfoshan Hospital of Shandong Province, Ji'nan, Shandong, China.
authors.forename: Ye
authors.initials: Y
authors.lastname: Wang
authors.affiliation: Department of Cardiology, Qianfoshan Hospital of Shandong Province, Ji'nan, Shandong, China.
authors.forename: Mei
authors.initials: M
authors.lastname: Xue
authors.affiliation: Department of Cardiology, Qianfoshan Hospital of Shandong Province, Ji'nan, Shandong, China.
authors.forename: Xiaolu
authors.initials: X
authors.lastname: Li
authors.affiliation: Department of Cardiology, Qianfoshan Hospital of Shandong Province, Ji'nan, Shandong, China.
authors.forename: Wenjuan
authors.initials: W
authors.lastname: Cheng
authors.affiliation: School of Medicine, Shandong University, Ji'nan, Shandong, China.
authors.forename: Yongli
authors.initials: Y
authors.lastname: Xuan
authors.affiliation: School of Medicine, Shandong University, Ji'nan, Shandong, China.
authors.forename: Jie
authors.initials: J
authors.lastname: Yin
authors.affiliation: School of Medicine, Shandong University, Ji'nan, Shandong, China.
authors.forename: Na
authors.initials: N
authors.lastname: Yang
authors.affiliation: Department of Cardiology, Qianfoshan Hospital of Shandong Province, Ji'nan, Shandong, China. Electronic address: yansuhua296@163.com.
authors.forename: Suhua
authors.initials: S
authors.lastname: Yan
mesh_terms: D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D004195:Disease Models, Animal; D006439:Hemodynamics / Q000187:drug effects; D008297:Male; D035683:MicroRNAs / Q000235:genetics / Q000378:metabolism*; D008954:Models, Biological; D009203:Myocardial Infarction / Q000235:genetics* / Q000503:physiopathology; D016328:NF-kappa B / Q000378:metabolism*; D024661:Potassium Channels, Inwardly Rectifying / Q000235:genetics / Q000378:metabolism*; D017208:Rats, Wistar; D015203:Reproducibility of Results; D015398:Signal Transduction / Q000187:drug effects*; D015854:Up-Regulation / Q000187:drug effects / Q000235:genetics; D000068756:Valsartan / Q000494:pharmacology*; D018487:Ventricular Dysfunction, Left / Q000235:genetics
chemical_list: C575188:KCNJ2 protein, rat; C547573:MIRN16 microRNA, rat; D035683:MicroRNAs; D016328:NF-kappa B; D024661:Potassium Channels, Inwardly Rectifying; D000068756:Valsartan
keywords: Kir2.1; Myocardial infarction; NF-κB; Rats; Valsartan; miR-16