title: Stem cell activation sustains hereditary hypertrophy in hamster cardiomyopathy.
abstract: Recent studies have documented the presence of stem cells within the myocardium and their role in the repair of ischaemic injury. Nevertheless, the pathogenic role of stem cells in non-ischaemic myocardial diseases, as well as the factors potentially responsible for their activation, is still under debate. The present study demonstrates the presence of an increased number of c-kit positive, MDR-positive, and Sca-1-positive stem cells within the myocardium of hereditary delta-SG null hamsters, a spontaneously occurring model of hypertrophic cardiomyopathy. When hamsters are 80 days old, ie at the 'hypertrophic' stage of the disease, but without haemodynamic overload, these cells associate with a multitude of cells co-expressing c-kit, cMet, GATA4, or MEF-2, and proliferating myocytes co-expressing myosin heavy chain, telomerase, ki67 and cyclin B. Furthermore, at the same animal age, the number of myocardial cells co-expressing c-kit and Flk-1, and the number of capillary vessels, is also amplified. In order to identify factors potentially responsible for stem cell activation, the myocardial expression of HGF and cMet and HGF plasma levels were evaluated, demonstrating their increase in 80-day-old delta-SG null hamsters. To demonstrate the possible ability of HGF to induce stem cell differentiation, bone-marrow-derived mesenchymal stem cells were challenged with HGF at the same plasma concentration observed in vivo. HGF induced cMet phosphorylation, and caused loss of stem cell features and overexpression of MEF-2, TEF1, and MHC. Our results demonstrate that stem cell activation occurs within the cardiomyopathic myocardium, very likely to maintain an efficient cardiac architecture. In this context, elevated levels of HGF might play a role in induction of stem cell commitment to the cardiomyocyte lineage and in cardioprotection through its anti-apoptotic action. Consistently, when cytokine levels declined to physiological concentrations, as in 150-day-old cardiomyopathic animals, myocardial apoptosis prevailed, prejudicing cardiac function.
authors.affiliation: Laboratorio di Cardiologia Molecolare e Cellulare, Università di Roma Tor Vergata, Rome, Italy.
authors.forename: Roberta
authors.initials: R
authors.lastname: Fiaccavento
authors.forename: Felicia
authors.initials: F
authors.lastname: Carotenuto
authors.forename: Marilena
authors.initials: M
authors.lastname: Minieri
authors.forename: Cristina
authors.initials: C
authors.lastname: Fantini
authors.forename: Giancarlo
authors.initials: G
authors.lastname: Forte
authors.forename: Arnaldo
authors.initials: A
authors.lastname: Carbone
authors.forename: Luciana
authors.initials: L
authors.lastname: Carosella
authors.forename: Roberto
authors.initials: R
authors.lastname: Bei
authors.forename: Laura
authors.initials: L
authors.lastname: Masuelli
authors.forename: Camilla
authors.initials: C
authors.lastname: Palumbo
authors.forename: Andrea
authors.initials: A
authors.lastname: Modesti
authors.forename: Maria
authors.initials: M
authors.lastname: Prat
authors.forename: Paolo
authors.initials: P
authors.lastname: Di Nardo
mesh_terms: D000818:Animals; D017209:Apoptosis; D002196:Capillaries / Q000473:pathology; D024741:Cardiomyopathy, Hypertrophic, Familial / Q000378:metabolism / Q000473:pathology*; D002454:Cell Differentiation / Q000187:drug effects; D002455:Cell Division; D002478:Cells, Cultured; D006224:Cricetinae; D004730:Endothelium, Vascular / Q000473:pathology; D006352:Heart Ventricles / Q000648:ultrastructure; D017228:Hepatocyte Growth Factor / Q000097:blood / Q000378:metabolism / Q000494:pharmacology; D059630:Mesenchymal Stem Cells / Q000187:drug effects / Q000473:pathology*; D032383:Myocytes, Cardiac / Q000648:ultrastructure
chemical_list: D017228:Hepatocyte Growth Factor