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- Title
Alamandine attenuates arterial remodelling induced by transverse aortic constriction in mice.
- Authors
de Souza-Neto, Fernando Pedro; de Morais e. Silva, Mario; de Carvalho Santuchi, Melissa; de Alcântara-Leonídio, Thaís Cristina; Motta-Santos, Daisy; Oliveira, Aline Cristina; Barrouin Melo, Marcos; Naves Canta, Giovanni; de Souza, Leandro Eziquiel; Costa Irigoyen, Maria Cláudia; Campagnole-Santos, Maria José; Guatimosim, Silvia; Souza Santos, Robson Augusto; Fernandes da Silva, Rafaela
- 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 withMas-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.
- Subjects
INFLAMMATORY mediators; VASCULAR remodeling; MATRIX metalloproteinases; TISSUE remodeling; MICE; ANGIOTENSIN I
- Publication
Clinical Science, 2019, Vol 133, Issue 5, p629
- ISSN
0143-5221
- Publication type
Article
- DOI
10.1042/CS20180547