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Título: | Discovery and characterization of Alamandine : a novel component of the Renin-Angiotensin system. |
Autor(es): | Lautner, Roberto Queiroga Villela, Daniel Campos Silva, Rodrigo Araújo Fraga da Silva, Neiva Caldeira Braga, Thiago Verano Fraga, Fabiana Costa Jankowski, Joachim Jankowski, Vera Sousa, Frederico Barros de Alzamora, Andréia Carvalho Soares, Everton Rocha Barbosa, Claudiane Maria Kjeldsen, Frank Oliveira, Aline Cristina Braga, Janaina Félix Savergnini, Silvia Silveira Quintão Etelvino, Gisele Maia Peluso, Antonio Augusto Bastos Silva, Danielle Gomes Passos Ferreira, Anderson José Alves, Fabiana Martins, Almir de Sousa Raizada, Mohan K. Paula, Renata Dutra de Santos, Daisy Motta Klempin, Friederike Pimenta, Adriano Monteiro de Castro Alenina, Natalia Sinisterra Millán, Ruben Dario Bader, Michael Santos, Maria José Campagnole dos Santos, Robson Augusto Souza dos |
Palavras-chave: | Antihypertensive treatment Cardiovascular system Hypertension Vasoactive peptides Vascular reactivity |
Data do documento: | 2013 |
Referência: | LAUTNER, R. Q. et al. Discovery and characterization of Alamandine: a novel component of the Renin-Angiotensin system. Circulation Research, v. 112, p. 1104, 2013. Disponível em: <http://circres.ahajournals.org/content/112/8/1104>. Acesso em: 19 fev. 2017. |
Resumo: | The renin–angiotensin system (RAS) is a key regulator of the cardiovascular system, electrolyte, and water balance. Here, we report identification and characterization of alamandine, a new heptapeptide generated by catalytic action of angiotensin-converting enzyme-2 angiotensin A or directly from angiotensin-(1–7). To characterize a novel component of the RAS, alamandine. Using mass spectrometry we observed that alamandine circulates in human blood and can be formed from angiotensin-(1–7) in the heart. Alamandine produces several physiological actions that resemble those produced by angiotensin-(1–7), including vasodilation, antifibrosis, antihypertensive, and central effects. Interestingly, our data reveal that its actions are independent of the known vasodilator receptors of the RAS, Mas, and angiotensin II type 2 receptor. Rather, we demonstrate that alamandine acts through the Mas-related G-protein–coupled receptor, member D. Binding of alamandine to Mas-related G-protein–coupled receptor, member D is blocked by D-Pro7-angiotensin-(1–7), the Mas-related G-protein–coupled receptor, member D ligand β-alanine and PD123319, but not by the Mas antagonist A-779. In addition, oral administration of an inclusion compound of alamandine/β-hydroxypropyl cyclodextrin produced a long-term antihypertensive effect in spontaneously hypertensive rats and antifibrotic effects in isoproterenol-treated rats. Alamandine had no noticeable proliferative or antiproliferative effect in human tumoral cell lines. The identification of these 2 novel components of the RAS, alamandine and its receptor, provides new insights for the understanding of the physiological and pathophysiological role of the RAS and may help to develop new therapeutic strategies for treating human cardiovascular diseases and other related disorders. |
URI: | http://www.repositorio.ufop.br/handle/123456789/7863 |
Link para o artigo: | http://circres.ahajournals.org/content/112/8/1104 |
DOI: | https://doi.org/10.1161/CIRCRESAHA.113.301077 |
ISSN: | 1524-4571 |
Aparece nas coleções: | DECBI - Artigos publicados em periódicos |
Arquivos associados a este item:
Arquivo | Descrição | Tamanho | Formato | |
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ARTIGO_DiscoveryCharacterizationAlamandine.pdf Until 2063-06-02 | 8,09 MB | Adobe PDF | Visualizar/Abrir | |
ARTIGO_DiscoveryCharacterizationCOORRECTION.pdf Restricted Access | 392,96 kB | Adobe PDF | Visualizar/Abrir |
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