title: Administration of pigment epithelium-derived factor inhibits left ventricular remodeling and improves cardiac function in rats with acute myocardial infarction.
abstract: Oxidative stress and inflammation are involved in cardiac remodeling after acute myocardial infarction (AMI). We have found that pigment epithelium-derived factor (PEDF) inhibits vascular inflammation through its anti-oxidative properties. However, effects of PEDF on cardiac remodeling after AMI remain unknown. We investigated whether PEDF could inhibit left ventricular remodeling and improve cardiac function in rats with AMI. AMI was induced in 8-week-old Sprague-Dawley rats by ligation of the left ascending coronary artery. Rats were treated intravenously with vehicle or 10 μg PEDF/100 g b.wt. every day for up to 2 weeks after AMI. Each rat was followed until 16 weeks of age. PEDF levels in infarcted areas and serum were significantly decreased at 1 week after AMI and remained low during the observational periods. PEDF administration inhibited apoptotic cell death and oxidative stress generation around the infarcted areas at 2 and 8 weeks after AMI. Further, PEDF injection suppressed cardiac fibrosis by reducing transforming growth factor-β and type III collagen expression, improved left ventricular ejection fraction, ameliorated diastolic dysfunction, and inhibited the increase in left ventricular mass index at 8 weeks after AMI. The present study demonstrated that PEDF could inhibit tissue remodeling and improve cardiac function in AMI rats. Substitution of PEDF may be a novel therapeutic strategy for cardiac remodeling after AMI.
authors.affiliation: Division of Cardio-Vascular Medicine, Department of Medicine, Kurume University School of Medicine, Kurume, Japan.
authors.forename: Shin-ichiro
authors.initials: S
authors.lastname: Ueda
authors.forename: Sho-ichi
authors.initials: S
authors.lastname: Yamagishi
authors.forename: Takanori
authors.initials: T
authors.lastname: Matsui
authors.forename: Yuko
authors.initials: Y
authors.lastname: Jinnouchi
authors.forename: Tsutomu
authors.initials: T
authors.lastname: Imaizumi
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D002465:Cell Movement / Q000187:drug effects; D005136:Eye Proteins / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D005355:Fibrosis; D006334:Heart Function Tests / Q000187:drug effects*; D006352:Heart Ventricles / Q000187:drug effects / Q000201:enzymology / Q000473:pathology / Q000503:physiopathology; D006439:Hemodynamics / Q000187:drug effects; D008264:Macrophages / Q000187:drug effects; D008297:Male; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D009203:Myocardial Infarction / Q000000981:diagnostic imaging / Q000188:drug therapy* / Q000201:enzymology / Q000503:physiopathology*; D009206:Myocardium / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects; D009414:Nerve Growth Factors / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D015843:Serpins / Q000008:administration & dosage* / Q000378:metabolism / Q000494:pharmacology* / Q000627:therapeutic use; D014463:Ultrasonography; D020257:Ventricular Remodeling / Q000187:drug effects*; D000099174:Pigment Epithelium-Derived Factor
chemical_list: D005136:Eye Proteins; D020778:Matrix Metalloproteinase 2; D009414:Nerve Growth Factors; D015843:Serpins; D000099174:Pigment Epithelium-Derived Factor