title: Improvement of cardiac function after implanting the osteopontin-derived peptide SVVYGLR in a hamster model of dilated cardiomyopathy.
abstract: OBJECTIVE
  Osteopontin is a multifunctional cytokine that can modulate a variety of cellular activities, such as fibrotic response and inflammation. Osteopontin-derived peptide Ser-Val-Val-Tyr-Gly-Leu-Arg (SVVYGLR; SV) induces angiogenesis and the expression of smooth muscle actin (SMA) in fibroblasts. In this study, we determined the effects of SV peptide on dilated cardiomyopathy (DCM).
  
  
  METHODS
  Gels containing SV peptide (SV group), a random SV peptide (GYRVLSV) (random group) or a simple phosphate-buffered saline solution (PBS group) were transplanted on to the left ventricular (LV) anterior wall of a DCM hamster model. A control group simply underwent chest opening and closing. We used echocardiography to measure cardiac function before gel implantation (week 0) and 2, 4, 6 and 8 weeks after gel implantation. Changes in histology and myocardial remodelling were evaluated 8 weeks after the gel implantation.
  
  
  RESULTS
  At 8 weeks post-treatment, the SV group had significantly better maintained cardiac function compared with the other groups. Histological analysis showed that LV chamber dilatation and cardiomyocyte hypertrophy were significantly attenuated, and the distribution of SMA-positive cells in the LV anterior wall area was greater in the SV group. The capillary density in the epicardial aspect of the anterior wall in the SV group was also significantly increased, indicating that the SV peptide released from the implanted gel had promoted angiogenesis. Furthermore, Western blotting and histological analyses showed that the level of expression of collagen type III at the gel-implanted anterior wall in the SV group was significantly increased, and the type III/type I collagen ratio was higher in the SV group than in the control or PBS groups.
  
  
  CONCLUSIONS
  SV peptide treatment improved cardiac function, and inhibited the dilatation of the LV chamber and cardiomyocyte hypertrophy. By inducing the differentiation of fibroblasts to SMA-positive muscle-like cells and increasing type III collagen, SV peptide conferred a contractile property on the gel-implanted wall. We believe that the SVVYGLR peptide treatment could be used as a bridge to a left ventricular assist device and heart transplantation and for cardiac regeneration therapy without cell transplantation in the future.
authors.affiliation: Department of Cardiovascular Pathology, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Yoko
authors.initials: Y
authors.lastname: Mizuno
authors.affiliation: Department of Cardiovascular Pathology, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Uchinaka
authors.affiliation: Department of Cardiovascular Pathology, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Yoshihito
authors.initials: Y
authors.lastname: Horii
authors.affiliation: Department of Molecular Pathology, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Seiji
authors.initials: S
authors.lastname: Mori
authors.affiliation: Department of Molecular Pathology, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Hamada
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.affiliation: Medical Centre of Translational Research, Osaka University Hospital, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.affiliation: Department of Cardiovascular Surgery, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.affiliation: Department of Molecular Pathology, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
authors.affiliation: Department of Cardiovascular Pathology, Division of Health Sciences, Osaka University Graduate School of Medicine, Suita, Japan kawaguch@sahs.med.osaka-u.ac.jp.
authors.forename: Naomasa
authors.initials: N
authors.lastname: Kawaguchi
mesh_terms: D000287:Administration, Topical; D043925:Angiogenesis Inducing Agents / Q000008:administration & dosage*; D000818:Animals; D002311:Cardiomyopathy, Dilated / Q000188:drug therapy* / Q000503:physiopathology; D006224:Cricetinae; D004195:Disease Models, Animal; D005782:Gels / Q000008:administration & dosage; D006352:Heart Ventricles / Q000187:drug effects*; D008297:Male; D009206:Myocardium / Q000378:metabolism; D009842:Oligopeptides / Q000008:administration & dosage*; D053495:Osteopontin / Q000378:metabolism; D016896:Treatment Outcome
chemical_list: D043925:Angiogenesis Inducing Agents; D005782:Gels; D009842:Oligopeptides; C586051:SVVYGLR peptide; D053495:Osteopontin
keywords: Collagen type III; Dilated cardiomyopathic hearts; Osteopontin-derived peptide SVVYGLR; Smooth muscle actin