title: Fibroblasts from human postmyocardial infarction scars acquire properties of cardiomyocytes after transduction with a recombinant myocardin gene.
abstract: Myocardial scar formation impairs heart function by inducing cardiac remodeling, decreasing myocardial compliance, and compromising normal electrical conduction. Conversion of myocardial scar fibroblasts (MSFs) into (functional) cardiomyocytes may be an effective alternative treatment to limit loss of cardiac performance after myocardial injury. In this study, we investigated whether the phenotype of MSFs can be modified by gene transfer into cells with properties of cardiomyocytes. To this end, fibroblasts from postmyocardial infarction scars of human left ventricles were isolated and characterized by cell biological, immunological, and molecular biological assays. Cultured human MSFs express GATA4 and connexin 43 and display adipogenic differentiation potential. Infection of human MSFs with a lentivirus vector encoding the potent cardiogenic transcription factor myocardin renders them positive for a wide variety of cardiomyocyte-specific proteins, including sarcomeric components, transcription factors, and ion channels, and induces the expression of several smooth muscle marker genes. Forced myocardin expression also endowed human MSFs with the ability to transmit an action potential and to repair an artificially created conduction block in cardiomyocyte cultures. These finding indicate that in vivo myocardin gene transfer may potentially limit cardiomyocyte loss, myocardial fibrosis, and disturbances in electrical conduction caused by myocardial infarction.
authors.affiliation: Department of Cardiology, Leiden University Medical Center, P.O. Box 9600, 2300 RC Leiden, The Netherlands.
authors.forename: John
authors.initials: J
authors.lastname: van Tuyn
authors.forename: Daniël A
authors.initials: DA
authors.lastname: Pijnappels
authors.forename: Antoine A F
authors.initials: AA
authors.lastname: de Vries
authors.forename: Ingrid
authors.initials: I
authors.lastname: de Vries
authors.forename: Ietje
authors.initials: I
authors.lastname: van der Velde-van Dijke
authors.forename: Shoshan
authors.initials: S
authors.lastname: Knaän-Shanzer
authors.forename: Arnoud
authors.initials: A
authors.lastname: van der Laarse
authors.forename: Martin J
authors.initials: MJ
authors.lastname: Schalij
authors.forename: Douwe E
authors.initials: DE
authors.lastname: Atsma
mesh_terms: D050156:Adipogenesis; D000818:Animals; D015415:Biomarkers / Q000378:metabolism; D002454:Cell Differentiation / Q000502:physiology*; D002478:Cells, Cultured; D002921:Cicatrix; D004553:Electric Conductivity; D005347:Fibroblasts / Q000166:cytology / Q000502:physiology*; D005786:Gene Expression Regulation; D005822:Genetic Vectors / Q000235:genetics / Q000378:metabolism; D006367:HeLa Cells; D006329:Heart Conduction System / Q000502:physiology; D006352:Heart Ventricles / Q000166:cytology / Q000473:pathology; D006801:Humans; D016086:Lentivirus / Q000235:genetics / Q000378:metabolism; D009203:Myocardial Infarction / Q000473:pathology*; D009206:Myocardium / Q000166:cytology / Q000473:pathology; D032383:Myocytes, Cardiac / Q000166:cytology / Q000502:physiology*; D009687:Nuclear Proteins / Q000235:genetics* / Q000378:metabolism; D010012:Osteogenesis; D010641:Phenotype; D011401:Promoter Regions, Genetic; D051381:Rats; D015534:Trans-Activators / Q000235:genetics* / Q000378:metabolism; D014157:Transcription Factors / Q000378:metabolism; D014161:Transduction, Genetic; D000099251:Myocardin
chemical_list: D015415:Biomarkers; D009687:Nuclear Proteins; D015534:Trans-Activators; D014157:Transcription Factors; D000099251:Myocardin