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Angiotensin-(1-7) receptor Mas is an essential modulator of extracellular matrix protein expression in the heart

Item Type:Article
Title:Angiotensin-(1-7) receptor Mas is an essential modulator of extracellular matrix protein expression in the heart
Creators Name:Gava, E. and de Castro, C.H. and Ferreira, A.J. and Colleta, H. and Melo, M.B. and Alenina, N. and Bader, M. and Oliveira, L.A. and Santos, R.A.S. and Kitten, G.T.
Abstract:In this study we investigated the effects of genetic deletion of the Angiotensin-(1-7) receptor Mas or the Angiotensin II receptor AT(2) on the expression of specific extracellular matrix (ECM) proteins in atria, right ventricles and atrioventricular (AV) valves of neonatal and adult mice. Quantification of collagen types I, III and VI and fibronectin was performed using immunofluorescence-labeling and confocal microscopy. Picrosirius red staining was used for the histological assessment of the overall collagen distribution pattern. ECM proteins, metalloproteinases (MMP), ERK1/2 and p38 levels were quantified by western blot analysis. Gelatin zymography was used to evaluate the activity of MMP-2 and MMP-9. We observed that the relative levels of collagen types I and III and fibronectin are significantly higher in both the right ventricle and AV valves of neonatal Mas(-/-) mouse hearts (e.g., collagen type I: 85.28±6.66 vs 43.50±4.41 arbitrary units in the right ventricles of Mas(+/+) mice). Conversely, the level of collagen type VI was lower in the right ventricle and AV valves of Mas(-/-) mice. Adult Mas(-/-) mouse hearts presented similar patterns as observed in neonates. No significant differences in ECM protein level were detected in atria. Likewise, no changes in ECM levels were observed in AT(2) knockout mouse hearts. Although deletion of Mas induced a significant reduction in the level of the active form of MMP-2 in neonate hearts and a reduction of both MMP-2 and MMP-9 in adult Mas(-/-) mice, no significant differences were observed in MMP enzymatic activities when compared to controls. The levels of the active, phosphorylated forms of ERK1/2 and p38 were higher in hearts of both neonatal and adult Mas(-/-) mice. These observations suggest that Mas is involved in the selective expression of specific ECM proteins within both the ventricular myocardium and AV valves. The changes in the ECM profile may alter the connective tissue framework and contribute to the decreased cardiac performance observed in Mas(-/-) mice.
Keywords:Angiotensin, Renin-Angiotensin System, Fibrosis, Connective Tissue, Extracellular Matrix, Mas Receptor, Animals, Mice
Source:Regulatory Peptides
ISSN:0167-0115
Publisher:Elsevier (The Netherlands)
Volume:175
Number:1-3
Page Range:30-42
Date:10 April 2012
Official Publication:https://doi.org/10.1016/j.regpep.2012.01.001
PubMed:View item in PubMed

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