title: Transplantation of myoblast sheets that secrete the novel peptide SVVYGLR improves cardiac function in failing hearts.
abstract: OBJECTIVE
  Transplantation of myoblast sheets is a promising therapy for enhancing cardiac function after heart failure. We have previously demonstrated that a 7-amino-acid sequence (Ser-Val-Val-Tyr-Gly-Leu-Arg) derived from osteopontin (SV peptide) induces angiogenesis. In this study, we evaluated the long-term therapeutic effects of myoblast sheets secreting SV in a rat infarction model.
  
  
  RESULTS
  Two weeks after ligation of the left anterior descending coronary artery, the animals were divided into the following three groups: a group transplanted with wild-type rat skeletal myoblast sheets (WT-rSkMs); a group transplanted with SV-secreting myoblast sheets (SV-rSkMs); and a control group (ligation only). We evaluated cardiac function, histological changes, and smooth muscle actin (SMA) expression through transforming growth factor-β (TGF-β) signalling. The ejection fraction and fractional shortening were significantly better, and the enlargement of end-systolic volume was also significantly attenuated in the SV-rSkM group. Left ventricular remodelling, including fibrosis and hypertrophy, was significantly attenuated in the SV-rSkM group, and SV secreted by the myoblast sheets promoted angiogenesis in the infarcted border area. Furthermore, many clusters of SMA-positive cells were observed in the infarcted areas in the SV-rSkM group. In vitro SMA expression was increased when SV was added to the isolated myocardial fibroblasts. Moreover, SV bound to the TGF-β receptor, and SV treatment activated TGF-β receptor-Smad signalling.
  
  
  CONCLUSIONS
  The SV-secreting myoblast sheets facilitate a long-term improvement in cardiac function. The SV can induce differentiation of fibroblasts to myofibroblasts via TGF-β-Smad signalling. This peptide could possibly be used as a bridge to heart transplantation or as an ideal peptide drug for cardiac regeneration therapy.
authors.affiliation: Department of Molecular Pathology, Osaka University Graduate School of Medicine, Suita, Japan.
authors.forename: Ayako
authors.initials: A
authors.lastname: Uchinaka
authors.forename: Naomasa
authors.initials: N
authors.lastname: Kawaguchi
authors.forename: Yoshinosuke
authors.initials: Y
authors.lastname: Hamada
authors.forename: Seiji
authors.initials: S
authors.lastname: Mori
authors.forename: Shigeru
authors.initials: S
authors.lastname: Miyagawa
authors.forename: Atsuhiro
authors.initials: A
authors.lastname: Saito
authors.forename: Yoshiki
authors.initials: Y
authors.lastname: Sawa
authors.forename: Nariaki
authors.initials: N
authors.lastname: Matsuura
mesh_terms: D000199:Actins / Q000378:metabolism; D000818:Animals; D004195:Disease Models, Animal; D005355:Fibrosis; D015316:Genetic Therapy; D057809:HEK293 Cells; D006333:Heart Failure / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000503:physiopathology / Q000628:therapy*; D006801:Humans; D008297:Male; D032448:Myoblasts, Skeletal / Q000378:metabolism / Q000637:transplantation*; D009206:Myocardium / Q000378:metabolism* / Q000473:pathology; D058628:Myofibroblasts / Q000378:metabolism / Q000473:pathology; D018995:Myosin Heavy Chains / Q000378:metabolism; D018919:Neovascularization, Physiologic; D009842:Oligopeptides / Q000096:biosynthesis* / Q000235:genetics; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism; D051381:Rats; D011917:Rats, Inbred Lew; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta / Q000378:metabolism; D020127:Recovery of Function; D012038:Regeneration; D051785:Smad Proteins / Q000378:metabolism; D024745:Smooth Muscle Myosins / Q000378:metabolism; D013318:Stroke Volume; D013997:Time Factors; D014162:Transfection; D016212:Transforming Growth Factor beta / Q000378:metabolism; D016277:Ventricular Function, Left; D017725:Ventricular Pressure; D020257:Ventricular Remodeling
chemical_list: D000199:Actins; D018995:Myosin Heavy Chains; D009842:Oligopeptides; D017346:Protein Serine-Threonine Kinases; D000077294:Receptor, Transforming Growth Factor-beta Type II; D018125:Receptors, Transforming Growth Factor beta; D051785:Smad Proteins; D024745:Smooth Muscle Myosins; D016212:Transforming Growth Factor beta; C586051:SVVYGLR peptide; C498862:Acta2 protein, rat
keywords: Cell therapy; Myocardial infarction; Myofibroblats; Peptides; Transforming growth factor-β