Dipeptidyl Peptidase 4 Inhibition Ameliorates Chronic Kidney Disease in a Model of Salt-Dependent Hypertension

Autor: Donato Cappetta, Loreta Pia Ciuffreda, Anna Cozzolino, Grazia Esposito, Cristina Scavone, Luigi Sapio, Silvio Naviglio, Domenico D'Amario, Filippo Crea, Francesco Rossi, Liberato Berrino, Antonella De Angelis, Konrad Urbanek, SAPIO, Luigi
Přispěvatelé: Cappetta, D, Ciuffreda, Lp, Cozzolino, A, Esposito, G, Scavone, C, Sapio, L, Naviglio, S, D’Amario, D, Crea, F, Rossi, F, Berrino, L, De Angelis, A, Urbanek, K, Cappetta, Donato, Loreta Pia Ciuffreda, Anna, Cozzolino, Grazia, Esposito, Scavone, Cristina, Luigi, Sapio, Naviglio, Silvio, Domenico, D'Amario, Filippo, Crea, Rossi, Francesco, Berrino, Liberato, DE ANGELIS, Antonella, Konrad, Urbanek, Sapio, Luigi
Jazyk: angličtina
Rok vydání: 2019
Předmět:
0301 basic medicine
Aging
medicine.medical_specialty
Article Subject
Macrophage polarization
Renal function
Cardiorenal syndrome
030204 cardiovascular system & hematology
Kidney
Kidney Function Tests
medicine.disease_cause
Models
Biological
Biochemistry
Glucagon-Like Peptide-1 Receptor
03 medical and health sciences
0302 clinical medicine
Glucagon-Like Peptide 1
Internal medicine
medicine
Animals
lcsh:QH573-671
Renal Insufficiency
Chronic
Sodium Chloride
Dietary
Endothelial dysfunction
Inflammation
Dipeptidyl-Peptidase IV Inhibitors
Rats
Inbred Dahl
lcsh:Cytology
business.industry
Endothelial Cells
Cell Biology
General Medicine
medicine.disease
Fibrosis
Hypertensive heart disease
Disease Models
Animal
Oxidative Stress
Phenotype
030104 developmental biology
Endocrinology
medicine.anatomical_structure
Nitrosative Stress
Hypertension
business
Oxidative stress
Research Article
Signal Transduction
Kidney disease
Zdroj: Oxidative Medicine and Cellular Longevity, Vol 2019 (2019)
Oxidative Medicine and Cellular Longevity
ISSN: 1942-0900
DOI: 10.1155/2019/8912768
Popis: Cardiovascular diseases frequently coexist with chronic kidney disease that constitutes a major determinant of outcome in patients with heart failure. Dysfunction of both organs is related to chronic inflammation, endothelial dysfunction, oxidative stress, and fibrosis. Widespread expression of serine protease DPP4 that degrades varieties of substrates suggests its involvement in numerous physiological processes. In this study, we tested the effects of selective DPP4 inhibition on the progression of renal disease in a nondiabetic model of hypertensive heart disease using Dahl salt-sensitive rats. Chronic DPP4 inhibition positively affected renal function with a significant reduction in albuminuria and serum creatinine. DPP4 inhibition attenuated the inflammatory component by reducing the expression of NF-κB, TNFα, IL-1β, IL-6, and MCP-1. Kidney macrophages expressed GLP-1R, and DPP4 inhibition promoted macrophage polarization toward the anti-inflammatory M2 phenotype. Finally, high degrees of NADPH oxidase 4 expression and oxidation of nucleic acids, lipids, and proteins were reduced upon DPP4 inhibition. Our study provides evidence of renoprotection by DPP4 inhibition in a nondiabetic hypertension-induced model of chronic cardiorenal syndrome, indicating that DPP4 pathway remains a valid object to study in the context of chronic multiorgan diseases.
Databáze: OpenAIRE
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