title: I(f) current channel inhibitor (ivabradine) deserves cardioprotective effect via down-regulating the expression of matrix metalloproteinase (MMP)-2 and attenuating apoptosis in diabetic mice.
abstract: BACKGROUND
  Ivabradine (IVBD), a novel I(f)-channel inhibitor and specific heart rate-lowering agent, is known to have anti-oxidative activity that promotes endothelial function. However, the molecular mechanism through which IVBD acts on cardiac function has yet to be elucidated, especially in experimental diabetic animals.
  
  
  METHODS
  For this reason, twenty diabetic mice were randomly assigned to IVBD-treated (10 mg/kg/day) and control (saline) groups. After a 3-month treatment, microarray assay was performed to identify differentia expressed genes, and cardiac function was measured by echocardiography, with subsequent immunohistochemistry analysis and western blotting.
  
  
  RESULTS
  Our results showed that ivabradine treatment attenuated the expression and staining score of matrix metalloproteinase (MMP)-2, induced the dephosphorylation of caspase 3, BAX and MMP-2, and enhanced the phosphorylation of NF-κB. Ivabradine treatment led to a significant improvement in cardiac function.
  
  
  CONCLUSIONS
  Ivabradine significantly improved cardiac function by attenuating apoptosis and inhibiting the expression and activity of MMP-2 in diabetic mice, which underscored the novel clinical implications of ivabradine for diabetic patients.
authors.affiliation: Department of Cardiology, Nanjing First Hospital, Nanjing Medical University, 68 Changle Road, Nanjing 210006, China. chmengx@126.com.
authors.forename: Shao-Liang
authors.initials: SL
authors.lastname: Chen
authors.forename: Zuo-Ying
authors.initials: ZY
authors.lastname: Hu
authors.forename: Guang-Feng
authors.initials: GF
authors.lastname: Zuo
authors.forename: Ming-Hui
authors.initials: MH
authors.lastname: Li
authors.forename: Bin
authors.initials: B
authors.lastname: Li
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects*; D001552:Benzazepines / Q000494:pharmacology*; D002316:Cardiotonic Agents / Q000494:pharmacology*; D053148:Caspase 3 / Q000378:metabolism; D002478:Cells, Cultured; D003920:Diabetes Mellitus / Q000175:diagnosis / Q000188:drug therapy* / Q000235:genetics; D058065:Diabetic Cardiomyopathies / Q000201:enzymology / Q000235:genetics / Q000473:pathology / Q000503:physiopathology / Q000517:prevention & control*; D004195:Disease Models, Animal; D015536:Down-Regulation; D000077550:Ivabradine; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000235:genetics / Q000378:metabolism*; D051379:Mice; D032383:Myocytes, Cardiac / Q000187:drug effects* / Q000201:enzymology / Q000473:pathology; D016328:NF-kappa B / Q000378:metabolism; D010766:Phosphorylation; D020127:Recovery of Function; D015398:Signal Transduction / Q000187:drug effects; D016277:Ventricular Function, Left / Q000187:drug effects; D051028:bcl-2-Associated X Protein / Q000378:metabolism
chemical_list: C494827:Bax protein, mouse; D001552:Benzazepines; D002316:Cardiotonic Agents; D016328:NF-kappa B; D051028:bcl-2-Associated X Protein; D000077550:Ivabradine; C505409:Casp3 protein, mouse; D053148:Caspase 3; D020778:Matrix Metalloproteinase 2; C522362:Mmp2 protein, mouse