Serelaxin attenuates renal inflammation and fibrosis in a mouse model of dilated cardiomyopathy.
Exp Physiol
; 103(12): 1593-1602, 2018 12.
Article
em En
| MEDLINE
| ID: mdl-30311699
ABSTRACT
NEW FINDINGS:
What is the central question of this study? The aim was to determine the renoprotective effects of serelaxin in the setting of chronic heart failure. What are the main findings and its importance? Our data indicate that serelaxin can reduce renal fibrosis and inflammation in experimental heart failure. Currently, there are no effective treatments to rescue renal function in heart failure patients, and our data suggest that serelaxin might have the potential to reduce renal fibrosis and inflammation in heart failure. ABSTRACT Serelaxin has been demonstrated to attenuate renal fibrosis and inflammation in cardiorenal disease. In the present study, we tested the hypothesis that serelaxin can prevent the decline in renal function in dilated cardiomyopathy (DCM) by targeting renal fibrosis and inflammation. Male transgenic mice with DCM (n = 16) and their wild-type littermates (WT; n = 20) were administered either vehicle or serelaxin (500 µg kg-1 day-1 ; subcutaneous minipumps; 8 weeks). Cardiac function was assessed via echocardiography before and during the eighth week of serelaxin treatment. Renal function and inflammation as well as cardiac and renal fibrosis were assessed at the end of the study. Serelaxin had minimal effect on cardiac function (P ≥ 0.99). Tubulointerstitial and glomerular fibrosis were â¼3-fold greater in vehicle-treated DCM mice compared with vehicle-treated WT mice (P ≤ 0.001). Renal mRNA expression of Tnfα and Il1α were â¼4- and â¼3-fold greater, respectively, in vehicle-treated DCM mice compared with vehicle-treated WT mice (P ≤ 0.05). Tubulointerstitial and glomerular fibrosis were 46 and 45% less, respectively, in serelaxin-treated DCM mice than in vehicle-treated DCM mice (P ≤ 0.01). Renal cortical mRNA expression of Tnfα and Il1α were 56 and 58% less, respectively, in the former group compared with the latter (P ≤ 0.05). The urinary albumincreatinine ratio was â¼3-fold greater in vehicle-treated DCM mice compared with vehicle-treated WT mice (P = 0.02). The urinary albumincreatinine ratio was not significantly different between vehicle-treated DCM mice and serelaxin-treated DCM mice (P = 0.38). These data suggest that serelaxin can attenuate renal fibrosis and inflammation and has the potential to exert renoprotective effects in DCM.Palavras-chave
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Base de dados:
MEDLINE
Assunto principal:
Relaxina
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Cardiomiopatia Dilatada
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Síndrome Cardiorrenal
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Insuficiência Cardíaca
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Rim
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Anti-Inflamatórios
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Nefrite
Idioma:
En
Ano de publicação:
2018
Tipo de documento:
Article