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Clin Sci (Lond). 2019 Mar 1;133(5):629-643. doi: 10.1042/CS20180547. Print 2019 Mar 15.

Alamandine attenuates arterial remodelling induced by transverse aortic constriction in mice.

Author information

1
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil.
2
Department of Cardiopneumology, Faculty of Medicine, University of São Paulo, São Paulo, Brazil.
3
Department of Physiology and Biophysics, Federal University of Minas Gerais, Belo Horizonte, Brazil robsonsant@gmail.com.

Abstract

Aims: The renin-angiotensin system (RAS) plays an important role in the pathophysiology of vascular diseases, especially as a mediator of inflammation and tissue remodelling. Alamandine (Ala1-angiotensin-(1-7)) is a new biologically active peptide from the RAS, interacting with Mas-related G-protein-coupled receptor member D. Although a growing number of studies reveal the cardioprotective effects of alamandine, there is a paucity of data on its participation in vascular remodelling associated events. In the present study, we investigated the effects of alamandine on ascending aorta remodelling after transverse aortic constriction (TAC) in mice. Methods and results: C57BL/6J male mice were divided into the following groups: Sham (sham-operated), TAC (operated) and TAC+ALA (operated and treated with alamandine-HPβCD (2-Hydroxypropyl-β-cyclodextrin), 30 μg/kg/day, by gavage). Oral administration of alamandine for 14 days attenuated arterial remodelling by decreasing ascending aorta media layer thickness and the cells density in the adventitia induced by TAC. Alamandine administration attenuated ascending aorta fibrosis induced by TAC, through a reduction in the following parameters; total collagen deposition, expression collagen III and transforming growth factor-β (TGF-β) transcripts, matrix metalloproteinases (MMPs) activity and vascular expression of MMP-2. Importantly, alamandine decreased vascular expression of proinflammatory genes as CCL2, tumour necrosis factor α (TNF-α) and interleukin-1β (IL-1β), and was able to increase expression of MRC1 and FIZZ1, pro-resolution markers, after TAC surgery. Conclusion: Alamandine treatment attenuates vascular remodelling after TAC, at least in part, through anti-fibrotic and anti-inflammatory effects. Hence, this work opens new avenues for the use of this heptapeptide also as a therapeutic target for vascular disease.

KEYWORDS:

Alamandine; Aortic transverse constriction; Arterial remodelling; MrgD receptor; Renin-angiotensin system

PMID:
30737255
DOI:
10.1042/CS20180547

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