Circulating cathepsin-S levels correlate with GFR decline and sTNFR1 and sTNFR2 levels in mice and humans.
Sci Rep
; 7: 43538, 2017 02 27.
Article
em En
| MEDLINE
| ID: mdl-28240259
Cardiovascular complications determine morbidity/mortality in chronic kidney disease (CKD). We hypothesized that progressive CKD drives the release of cathepsin-S (Cat-S), a cysteine protease that promotes endothelial dysfunction and cardiovascular complications. Therefore, Cat-S, soluble tumor-necrosis-factor receptor (sTNFR) 1/2 and glomerular filtration rate (GFR) were measured in a CKD mouse model, a German CKD-cohort (MCKD, n = 421) and two Swedish community-based cohorts (ULSAM, n = 764 and PIVUS, n = 804). Association between Cat-S and sTNFR1/2/GFR was assessed using multivariable linear regression. In the mouse model, Cat-S and sTNFR1/2 concentrations were increased following the progressive decline of GFR, showing a strong correlation between Cat-S and GFR (r = -0.746, p < 0.001) and Cat-S and sTNFR1/sTNFR2 (r = 0.837/0.916, p < 0.001, respectively). In the human cohorts, an increase of one standard deviation of estimated GFR was associated with a decrease of 1.008 ng/ml (95%-confidence interval (95%-CI) -1.576-(-0.439), p < 0.001) in Cat-S levels in MCKD; in ULSAM and PIVUS, results were similar. In all three cohorts, Cat-S and sTNFR1/sTNFR2 levels were associated in multivariable linear regression (p < 0.001). In conclusion, as GFR declines Cat-S and markers of inflammation-related endothelial dysfunction increase. The present data indicating that Cat-S activity increases with CKD progression suggest that Cat-S might be a therapeutic target to prevent cardiovascular complications in CKD.
Texto completo:
1
Base de dados:
MEDLINE
Assunto principal:
Catepsinas
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Fatores de Troca do Nucleotídeo Guanina
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Receptores Tipo I de Fatores de Necrose Tumoral
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Receptores Tipo II do Fator de Necrose Tumoral
Tipo de estudo:
Diagnostic_studies
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Etiology_studies
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Prognostic_studies
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Risk_factors_studies
Limite:
Adult
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Aged
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Animals
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Female
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Humans
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Male
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Middle aged
País como assunto:
Europa
Idioma:
En
Ano de publicação:
2017
Tipo de documento:
Article