In:
Hypertension, Ovid Technologies (Wolters Kluwer Health), Vol. 70, No. suppl_1 ( 2017-09)
Abstract:
Recently, we described a new peptide of the RAS, the heptapeptide alamandine. Alamandine [Ala 1 -angiotensin-(1-7)] is formed from angiotensin-(1-7) by decarboxilation of the N-terminal Asp residue to Alanine or from the octapeptide angiotensin A (Ala 1 -Ang II) by removal of the Phe c-terminal residue by ACE2. Alamandine effects were independent of Angiotensin-(1-7) receptor Mas. The Mas-related G protein receptor member D (MrgD) was identified as the alamandine receptor. Although cardioprotective effects of alamandine similar to Ang-(1-7) have been described, the significance of this peptide in the heart function is still elusive. Objective: To evaluate the functional role of the alamandine receptor, MrgD, in the heart using MrgD-deficient mice. Methods: Primary cardiomyocytes were obtained from neonatal rats and mice with up to 72 hours of life. Cells were fixed, blocked, permeabilized and incubated with an anti-MrgD antibody, washed and incubated with a secondary antibody and Phalloidin. Slides were analysed using confocal microscopy. High-resolution echocardiography was performed in MrgD +/+ and MrgD -/- mice (12 weeks old, n=5-6) 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 (VevoStrain). Results: Immunofluorescence indicates that MrgD is present in cardiomyocytes, mainly in the perinuclear and nuclear region, with similar pattern in rats and mice. High resolution echocardiography showed left ventricular remodelling and dysfunction in MrgD-KO mice when compared to their controls. Strikingly, MrgD-deficient mice presented a pronounced dilated cardiomyopathy with a marked decrease in systolic function (EF: 34.39 ± 2.9 versus 66.49 ± 2.3 %; FS: 16.23 ± 0.6 versus 35.91 ± 1.8 %; EDV: WT = 46.47 ± 2.4 versus 81.15 ± 3.7; ESV: 15.41 ± 0.7 versus 53.21 ± 2.5). Conclusion: Alamandine MrgD receptor is expressed in cardiomyocytes and its deletion leads to a pronounced dilated cardiomyopathy indicating a major role for alamandine in the heart.
Type of Medium:
Online Resource
ISSN:
0194-911X
,
1524-4563
DOI:
10.1161/hyp.70.suppl_1.138
Language:
English
Publisher:
Ovid Technologies (Wolters Kluwer Health)
Publication Date:
2017
detail.hit.zdb_id:
2094210-2
