title: Mesenchymal stem cell therapy associated with endurance exercise training: Effects on the structural and functional remodeling of infarcted rat hearts.
abstract: We tested the effects of early mesenchymal stem cell (MSC) therapy associated with endurance exercise on the structural and functional cardiac remodeling of rats with myocardial infarctation (MI). Male Wistar rats (40 days old) were divided into 6 groups: control and exercise sham; control and exercise MI; and control and exercise MI MSC. MI was surgically induced and bone marrow-derived MSCs were immediately injected via caudal vein (concentration: 1 × 10(6 )cells). Twenty-four hours later ET groups exercised on a treadmill (5 days/week; 60 min/day; 60% of maximal running velocity) for 12 weeks. Structural and functional changes were determined by echocardiography. Contractility and intracellular global calcium ([Ca(2 +)]i) transient were measured in myocytes from the left ventricular (LV) non-infarcted area. Calcium regulatory proteins were measured by Western blot. MI increased (p < 0.05) heart, ventricular and LV weights and its ratios to body weight; LV internal dimension in diastole (LVID-D) and in systole (LVID-S) and LV free wall in diastole (LVFW-D), but reduced the thickness of interventricular septum in systole (IVS-S), ejection fraction (EF) and fractional shortening (FS). MI augmented (p < 0.05) the times to peak and to half relaxation of cell shortening as well as the amplitude of the [Ca(2 +)]i transient and the times to peak and to half decay. Early MSCs therapy restored LVFW-D, IVS-S and the amplitude and time to half decay of the [Ca(2 +)]i transient. Early endurance exercise intervention increased (p < 0.05) LVFW-S, IVS-S, EF and FS, and reduced the times to peak and to half relaxation of cell shortening, and the amplitude of the [Ca(2 +)]i transient. Exercise training also increased the expression of left ventricular SERCA2a and PLBser16. Nevertheless, the combination of these therapies did not cause additive effects. In conclusion, combining early MSCs therapy and endurance exercise does not potentiate the benefits of such treatments to structural and functional cardiac remodeling in infarcted rats.
authors.affiliation: Department of Physical Education, Exercise Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Victor Neiva
authors.initials: VN
authors.lastname: Lavorato
authors.affiliation: Department of Veterinary Medicine, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Ricardo Junqueira
authors.initials: RJ
authors.lastname: Del Carlo
authors.affiliation: Department of Physical Education, Exercise Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Daise Nunes Queiroz
authors.initials: DN
authors.lastname: da Cunha
authors.affiliation: Department of Veterinary Medicine, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Barbara Silva
authors.initials: BS
authors.lastname: Okano
authors.affiliation: Department of Physical Education, Exercise Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Felipe Gomes
authors.initials: FG
authors.lastname: Belfort
authors.affiliation: Departament of General Biology, Structural Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Juliana Silveira
authors.initials: JS
authors.lastname: de Freitas
authors.affiliation: School of Physical Education and Sport, Biochemistry and Molecular Biology Laboratory, Universidade de São Paulo (USP), São Paulo, São Paulo, Brazil.
authors.forename: Gloria de Fatima Alves
authors.initials: Gde F
authors.lastname: da Mota
authors.affiliation: Departament of General Biology, Structural Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Judson Fonseca
authors.initials: JF
authors.lastname: Quintão-Júnior
authors.affiliation: Department of Physical Education, Exercise Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Luis Henrique Lobo
authors.initials: LH
authors.lastname: Silame-Gomes
authors.affiliation: Department of Physical Education, Exercise Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Filipe Rios
authors.initials: FR
authors.lastname: Drummond
authors.affiliation: Department of Physical Education, Exercise Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Miguel Araújo
authors.initials: MA
authors.lastname: Carneiro-Júnior
authors.affiliation: School of Physical Education and Sport, Biochemistry and Molecular Biology Laboratory, Universidade de São Paulo (USP), São Paulo, São Paulo, Brazil.
authors.forename: Edilamar Menezes
authors.initials: EM
authors.lastname: de Oliveira
authors.affiliation: Veterinary Medicine, Universidade Vila Velha (UVV), Vila Velha, Espírito Santo, Brazil.
authors.forename: Betania Souza
authors.initials: BS
authors.lastname: Monteiro
authors.affiliation: Department of Physical Education, Exercise Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil.
authors.forename: Thales Nicolau
authors.initials: TN
authors.lastname: Prímola-Gomes
authors.affiliation: Department of Physical Education, Exercise Biology Laboratory, Universidade Federal de Viçosa (UFV), Viçosa, Minas Gerais, Brazil. Electronic address: anatali@ufv.br.
authors.forename: Antônio José
authors.initials: AJ
authors.lastname: Natali
mesh_terms: D000818:Animals; D002118:Calcium / Q000378:metabolism; D002135:Calcium-Binding Proteins / Q000235:genetics / Q000378:metabolism; D003971:Diastole; D004452:Echocardiography; D015870:Gene Expression; D008297:Male; D045164:Mesenchymal Stem Cell Transplantation; D059630:Mesenchymal Stem Cells / Q000166:cytology / Q000378:metabolism; D009200:Myocardial Contraction / Q000502:physiology; D009203:Myocardial Infarction / Q000235:genetics / Q000378:metabolism / Q000473:pathology / Q000628:therapy*; D009206:Myocardium / Q000378:metabolism / Q000473:pathology; D032383:Myocytes, Cardiac / Q000378:metabolism / Q000473:pathology; D010805:Physical Conditioning, Animal; D010807:Physical Endurance; D051381:Rats; D017208:Rats, Wistar; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases / Q000235:genetics / Q000378:metabolism; D013599:Systole; D020257:Ventricular Remodeling; D000099211:Phospholamban
chemical_list: D002118:Calcium; D002135:Calcium-Binding Proteins; D053498:Sarcoplasmic Reticulum Calcium-Transporting ATPases; D000099211:Phospholamban
keywords: Cardiomyocytes; Endurance training; Myocardial infarction; Stem cells