title: Original Research: ACE2 activator associated with physical exercise potentiates the reduction of pulmonary fibrosis.
abstract: The interstitial lung diseases are poorly understood and there are currently no studies evaluating the association of physical exercise with an ACE2 activator (DIZE) as a possible treatment for this group of diseases. We evaluate the effects of pharmacological treatment with an angiotensin-converting enzyme 2 activator drug, associated with exercise, on the pulmonary lesions induced by bleomycin. From the 96 male Balb/c mice used in the experiment, only 49 received 8 U/kg of bleomycin (BLM, intratracheally). The mice were divided into control (C) and bleomycin (BLM) groups, sedentary and trained (C-SED, C-EXE, BLM-SED, BLM-EXE), control and bleomycin and also sedentary and trained treated with diminazene (C-SED/E, C-EXE/E, BLM-SED/E, BLM-EXE/E). The animals were trained five days/week, 1 h/day with 60% of the maximum load obtained in a functional capacity test, for four weeks. Diminazene groups were treated (1 mg/kg, by gavage) daily until the end of the experiment. The lungs were collected 48 h after the training program, set in buffered formalin and investigated by Gomori's trichrome, immunohistochemistry of collagen type I, TGF-β1, beta-prolyl-4-hydroxylase, MMP-1 and -2. The BLM-EXE/E group obtained a significant increase in functional capacity, reduced amount of fibrosis and type I collagen, decreased expression of TGF-β1and beta-prolyl-4-hydroxylase and an increase of metalloproteinase -1, -2 when compared with the other groups. The present research shows, for the first time, that exercise training associated with the activation of ACE2 potentially reduces pulmonary fibrosis.
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, CEP 31 270-901, Brasil.
authors.forename: Luana O
authors.initials: LO
authors.lastname: Prata
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, CEP 31 270-901, Brasil.
authors.forename: Carolina R
authors.initials: CR
authors.lastname: Rodrigues
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, CEP 31 270-901, Brasil.
authors.forename: Jéssica M
authors.initials: JM
authors.lastname: Martins
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, CEP 31 270-901, Brasil.
authors.forename: Paula C
authors.initials: PC
authors.lastname: Vasconcelos
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, CEP 31 270-901, Brasil.
authors.forename: Fabrício Marcus S
authors.initials: FM
authors.lastname: Oliveira
authors.affiliation: Departamento de Morfologia da Universidade Federal de Minas Gerais, Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, CEP 31 270-901, Brasil.
authors.forename: Anderson J
authors.initials: AJ
authors.lastname: Ferreira
authors.affiliation: Faculdade Ciências Médicas, Belo Horizonte, Minas Gerais, CEP 30110-130, Brasil.
authors.forename: Maria da Glória
authors.initials: MD
authors.lastname: Rodrigues-Machado
authors.affiliation: Departamento de Patologia Geral, Instituto de Ciências Biológicas da Universidade Federal de Minas Gerais, Belo Horizonte, Minas Gerais, CEP 31 270-901, Brasil caliari@icb.ufmg.br.
authors.forename: Marcelo V
authors.initials: MV
authors.lastname: Caliari
mesh_terms: D000085962:Angiotensin-Converting Enzyme 2; D000818:Animals; D024042:Collagen Type I / Q000378:metabolism; D004133:Diminazene / Q000494:pharmacology*; D004195:Disease Models, Animal; D008168:Lung / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D008297:Male; D020781:Matrix Metalloproteinase 1 / Q000378:metabolism; D020778:Matrix Metalloproteinase 2 / Q000378:metabolism; D008807:Mice, Inbred BALB C; D007703:Peptidyl-Dipeptidase A / Q000378:metabolism*; D010805:Physical Conditioning, Animal / Q000502:physiology*; D010807:Physical Endurance / Q000187:drug effects; D011658:Pulmonary Fibrosis / Q000188:drug therapy / Q000503:physiopathology / Q000628:therapy*
chemical_list: D024042:Collagen Type I; D007703:Peptidyl-Dipeptidase A; C000705328:Ace2 protein, mouse; D000085962:Angiotensin-Converting Enzyme 2; D020778:Matrix Metalloproteinase 2; D020781:Matrix Metalloproteinase 1; D004133:Diminazene
keywords: ACE2 activation; MMPs; TGF-β; beta-prolyl-4-hydroxylase; physical exercise; type I collagen