Adenine-Induced Nephropathy Reduces Atherosclerosis in ApoE Knockout Mice.
Biomolecules
; 12(8)2022 08 19.
Article
en En
| MEDLINE
| ID: mdl-36009040
BACKGROUND: Cardiovascular events are the main cause of death in patients with chronic kidney disease. We hypothesize that the protective effects of renal cholesterol and vitamin D3 metabolism are lost under this condition. Nephropathy was induced by adenine in Apolipoprotein E knockout mice. The atherosclerotic phenotype was compared to mice with normal renal function. METHODS: Mice were fed a western diet ±0.15% adenine. Urine and feces were collected to assess renal function and fecal output. Atherosclerosis, serum lipoprotein composition and functionality, hepatic lipids, and expression of genes involved in lipid metabolism, vitamin D3 and Na+ homeostasis, were assessed. Bones were analyzed by microCT. RESULTS: Mice fed with adenine showed enhanced urinary Na+, Ca2+, and Pi excretion, reduced urinary pH, UreaUrine/UreaSerum, and CreatinineUrine/CreatinineSerum ratios. They developed less atherosclerosis. Lipoproteins in serum and hepatic lipids remained unchanged. Cholesterol efflux increased. Fecal output of cholesteryl ester and triglycerides increased. In the liver, mRNA levels of Cyp27a1, Cyp7a1, and Scarb1 increased; in the kidneys, Slc9a3, Slc12a3, Vdr, and Cyp24a1 decreased. Adenine increased cholesterol efflux in vitro. Tibias were shorter. CONCLUSION: Adenine induced tubular damage and was athero-protective because of enhanced cholesterol efflux and lipids elimination in feces. Bone growth was also affected.
Palabras clave
Texto completo:
1
Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Adenina
/
Aterosclerosis
Límite:
Animals
Idioma:
En
Revista:
Biomolecules
Año:
2022
Tipo del documento:
Article
País de afiliación:
Suiza
Pais de publicación:
Suiza