title: Endogenous resident c-Kit cardiac stem cells increase in mice with an exercise-induced, physiologically hypertrophied heart.
abstract: Physical activity evokes well-known adaptations in the cardiovascular system. Although exercise training induces cardiac remodeling, whether multipotent stem cells play a functional role in the hypertrophic process remains unknown. To evaluate this possibility, C57BL/6 mice were subjected to swimming training aimed at achieving cardiac hypertrophy, which was morphologically and electrocardiographically characterized. Subsequently, c-Kit(+)Lin(-) and Sca-1(+)Lin(-) cardiac stem cells (CSCs) were quantified using flow cytometry while cardiac muscle-derived stromal cells (CMSCs, also known as cardiac-derived mesenchymal stem cells) were assessed using in vitro colony-forming unit fibroblast assay (CFU-F). Only the number of c-Kit(+)Lin(-) cells increased in the hypertrophied heart. To investigate a possible extracardiac origin of these cells, a parabiotic eGFP transgenic/wild-type mouse model was used. The parabiotic pairs were subjected to swimming, and the wild-type heart in particular was tested for eGFP(+) stem cells. The results revealed a negligible number of extracardiac stem cells in the heart, allowing us to infer a cardiac origin for the increased amount of detected c-Kit(+) cells. In conclusion, the number of resident Sca-1(+)Lin(-) cells and CMSCs was not changed, whereas the number of c-Kit(+)Lin(-) cells was increased during physiological cardiac hypertrophy. These c-Kit(+)Lin(-) CSCs may contribute to the physiological cardiac remodeling that result from exercise training.
authors.affiliation: Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Camila Ferreira
authors.initials: CF
authors.lastname: Leite
authors.affiliation: Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Carolina Salomão
authors.initials: CS
authors.lastname: Lopes
authors.affiliation: Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Angélica Cristina
authors.initials: AC
authors.lastname: Alves
authors.affiliation: Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Caroline Santos Capitelli
authors.initials: CS
authors.lastname: Fuzaro
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Marcos Vinícius
authors.initials: MV
authors.lastname: Silva
authors.affiliation: Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Lucas Felipe de
authors.initials: LF
authors.lastname: Oliveira
authors.affiliation: Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Lidiane Pereira
authors.initials: LP
authors.lastname: Garcia
authors.affiliation: Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Thaís Soares
authors.initials: TS
authors.lastname: Farnesi
authors.affiliation: Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Marília Beatriz de
authors.initials: MB
authors.lastname: Cuba
authors.affiliation: Department of Morphology, Institute for Biological and Natural Sciences, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Lenaldo Branco
authors.initials: LB
authors.lastname: Rocha
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Virmondes
authors.initials: V
authors.lastname: Rodrigues
authors.affiliation: Department of Microbiology, Immunology and Parasitology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil.
authors.forename: Carlo José Freire de
authors.initials: CJ
authors.lastname: Oliveira
authors.affiliation: Department of Biochemistry, Pharmacology, Physiology and Molecular Biology, Triângulo Mineiro Federal University, Praça Manoel Terra, 330, Centro, 38025-015 Uberaba, MG, Brazil. Electronic address: valdo@mednet.com.br.
authors.forename: Valdo José
authors.initials: VJ
authors.lastname: Dias da Silva
mesh_terms: D000818:Animals; D006332:Cardiomegaly / Q000000981:diagnostic imaging / Q000473:pathology* / Q000503:physiopathology*; D002448:Cell Adhesion; D002452:Cell Count; D003114:Colony-Forming Units Assay; D005434:Flow Cytometry; D049452:Green Fluorescent Proteins / Q000378:metabolism; D008297:Male; D008810:Mice, Inbred C57BL; D008822:Mice, Transgenic; D009206:Myocardium / Q000473:pathology*; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D019009:Proto-Oncogene Proteins c-kit / Q000378:metabolism*; D013234:Stem Cells / Q000166:cytology* / Q000378:metabolism*; D017154:Stromal Cells / Q000166:cytology; D013550:Swimming; D014463:Ultrasonography; D020257:Ventricular Remodeling
chemical_list: C485184:enhanced green fluorescent protein; D049452:Green Fluorescent Proteins; D019009:Proto-Oncogene Proteins c-kit