Genetic deletion of the alamandine receptor MrgD leads to dilated cardiomyopathy in mice

Item Type:	Article
Title:	Genetic deletion of the alamandine receptor MrgD leads to dilated cardiomyopathy in mice
Creators Name:	Oliveira, A.C. and Melo, M.B. and Motta-Santos, D. and Peluso, A.A. and Souza-Neto, F. and da Silva, R.F. and Almeida, J.F.Q. and Canta, G. and Reis, A.M. and Goncalves, G. and Cerri, G.G. and Coutinho, D. and de Jesus, I.C.G. and Guatimosim, S. and Linhares, N.D. and Alenina, N. and Bader, M. and Campagnole-Santos, M.J. and Santos, R.A.S.
Abstract:	We have recently described a new peptide of the renin angiotensin system, alamandine, a derivative of angiotensin-(1-7). The Mas-related G-protein coupled receptor member D (MrgD) was identified as its receptor. Although similar cardioprotective effects of alamandine to those of Ang-(1-7) have been described, the significance of this peptide in heart function is still elusive. We aimed to evaluate the functional role of the alamandine receptor, MrgD, in the heart, using MrgD-deficient mice. MrgD was localized in cardiomyocytes by immunofluorescence using confocal microscopy. High-resolution echocardiography was performed in WT and MrgD deficient mice (2 and 12 weeks old) under isoflurane anesthesia. Standard B-mode images were obtained in right and left parasternal long and short axis for morphological and functional assessment and evaluation of cardiac deformation. Additional heart function evaluation was performed using Langendorff isolated heart preparations and inotropic measurements of isolated cardiomyocytes. Immunofluorescence indicated that MrgD receptor is expressed in cardiomyocytes, mainly in the membrane, perinuclear and nuclear region. Echocardiography showed left ventricular remodeling and severe dysfunction in MrgD-deficient mice. Strikingly, MrgD-deficient mice presented a pronounced dilated cardiomyopathy with a marked decrease in systolic function. Echocardiographic changes were supported by the data obtained in isolated hearts and inotropic measurements in cardiomyocytes. Our data add new evidence for a major role for alamandine/MrgD in the hearth. Furthermore, our results indicate that we have identified a new gene implicated in dilated cardiomyopathy, unveiling a new target for translational approaches aimed to treat heart diseases.
Keywords:	Alamandine, Dilated Cardiomyopathy, Mas-Related G Protein-Coupled Receptor Member D, Animals, Mice
Source:	American Journal of Physiology Heart and Circulatory Physiology
ISSN:	0363-6135
Publisher:	American Physiological Society
Volume:	316
Number:	1
Page Range:	H123-H133
Date:	January 2019
Official Publication:	https://doi.org/10.1152/ajpheart.00075.2018
PubMed:	View item in PubMed

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