title: Exercise induces renin-angiotensin system unbalance and high collagen expression in the heart of Mas-deficient mice.
abstract: The renin-angiotensin system (RAS) is involved in the cardiac and vascular remodeling associated with cardiovascular diseases. Angiotensin (Ang) II/AT(1) axis is known to promote cardiac hypertrophy and collagen deposition. In contrast, Ang-(1-7)/Mas axis opposes Ang II effects in the heart producing anti-trophic and anti-fibrotic effects. Exercise training is known to induce cardiac remodeling with physiological hypertrophy without fibrosis. We hypothesize that cardiac remodeling induced by chronic exercise depends on the action of Ang-(1-7)/Mas axis. Thus, we evaluated the effect of exercise training on collagen deposition and RAS components in the heart of FVB/N mice lacking Mas receptor (Mas-KO). Male wild-type and Mas-KO mice were subjected to a moderate-intense swimming exercise training for 6 weeks. The left ventricle (LV) of the animals was sectioned and submitted to qRT-PCR and histological analysis. Circulating and tissue angiotensin peptides were measured by RIA. Sedentary Mas-KO presented a higher circulating Ang II/Ang-(1-7) ratio and an increased ACE2 expression in the LV. Physical training induced in Mas-KO and WT a similar cardiac hypertrophy accompanied by a pronounced increase in collagen I and III mRNA expression. Trained Mas-KO and trained WT presented increased Ang-(1-7) in the blood. However, only in trained-WT there was an increase in Ang-(1-7) in the LV. In summary, we showed that deletion of Mas in FVB/N mice produced an unbalance in RAS equilibrium increasing Ang II/AT(1) arm and inducing deleterious cardiac effects as deposition of extracellular matrix proteins. These data indicate that Ang-(1-7)/Mas axis is an important counter-regulatory mechanism in physical training mediate cardiac adaptations.
authors.affiliation: INCT NanoBioFar, Department of Physiology and Biophysics, Federal University of Minas Gerais (UFMG), Belo Horizonte, Minas Gerais, Brazil.
authors.forename: Gislaine G
authors.initials: GG
authors.lastname: Guimarães
authors.forename: Sérgio H S
authors.initials: SH
authors.lastname: Santos
authors.forename: Marilene L
authors.initials: ML
authors.lastname: Oliveira
authors.forename: Elizabeth P
authors.initials: EP
authors.lastname: Pimenta-Velloso
authors.forename: Daisy F
authors.initials: DF
authors.lastname: Motta
authors.forename: Almir S
authors.initials: AS
authors.lastname: Martins
authors.forename: Natalia
authors.initials: N
authors.lastname: Alenina
authors.forename: Michael
authors.initials: M
authors.lastname: Bader
authors.forename: Robson A S
authors.initials: RA
authors.lastname: Santos
authors.forename: Maria Jose
authors.initials: MJ
authors.lastname: Campagnole-Santos
mesh_terms: D000803:Angiotensin I / Q000378:metabolism; D000804:Angiotensin II / Q000378:metabolism; D000818:Animals; D003094:Collagen / Q000235:genetics / Q000378:metabolism*; D024042:Collagen Type I / Q000235:genetics / Q000378:metabolism; D024061:Collagen Type III / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D006321:Heart / Q000503:physiopathology*; D017379:Hypertrophy, Left Ventricular; D008297:Male; D051379:Mice; D018345:Mice, Knockout; D010446:Peptide Fragments / Q000378:metabolism; D010805:Physical Conditioning, Animal / Q000009:adverse effects*; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins / Q000235:genetics*; D043562:Receptors, G-Protein-Coupled / Q000235:genetics*; D012084:Renin-Angiotensin System / Q000502:physiology*; D020257:Ventricular Remodeling / Q000502:physiology
chemical_list: D024042:Collagen Type I; D024061:Collagen Type III; D010446:Peptide Fragments; D000090063:Proto-Oncogene Mas; D011518:Proto-Oncogene Proteins; D043562:Receptors, G-Protein-Coupled; D000804:Angiotensin II; D003094:Collagen; D000803:Angiotensin I; C118790:angiotensin I (1-7)