Recombinant Fc-Elabela fusion protein has extended plasma half-life andmitigates post-infarct heart dysfunction in rats.
Int J Cardiol
; 292: 180-187, 2019 10 01.
Article
em En
| MEDLINE
| ID: mdl-31101543
ABSTRACT
Activation of the apelin receptor, or APJ, by apelin is considered a therapeutic avenue for cardiovascular disease, including heart failure. Recently, a novel endogenous ligand for APJ named Elabela (ELA) has been discovered and is known to possess anti-heart failure activity in animal models. However, the short in vivo half-life of ELA constrains its clinical potential. To extend its half-life in vivo, we attempted to make IgG-Fc-ELA fusion proteins. We found that Fc-ELA-32 fusion proteins are cleaved during protein production, whereas Fc-ELA-21 fusion proteins are expressed intact, so we focused our studies on the latter. The Fc-ELA-21 fusion protein retained its functionality in vitro and had a half-life of approximately 44â¯h in circulation in mice after subcutaneous injection. Daily injection of the fusion protein in MI rats for 4â¯weeks significantly mitigated heart dysfunction with respect to hemodynamics. At the cellular and tissue levels, treatment of Fc-ELA-21 fusion protein significantly increased angiogenesis, promoted cardiomyocyte proliferation and reduced apoptosis and heart fibrosis near the infarct area. In comparison, ELA-21 had a half-life of 13â¯min and showed no significant cardioprotective activities. These data suggest that Fc-ELA-21 may be a potential therapeutic for heart failure.
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Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Recombinantes de Fusão
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Hormônios Peptídicos
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Infarto do Miocárdio
Limite:
Animals
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Humans
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Male
Idioma:
En
Revista:
Int J Cardiol
Ano de publicação:
2019
Tipo de documento:
Article
País de afiliação:
Estados Unidos