Scherler, Laeticia; Verouti, Sofia N; Ackermann, Daniel; Vogt, Bruno; Escher, Geneviève (2022). Adenine-Induced Nephropathy Reduces Atherosclerosis in ApoE Knockout Mice. Biomolecules, 12(8) MDPI 10.3390/biom12081147
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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.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
04 Faculty of Medicine > Department of Dermatology, Urology, Rheumatology, Nephrology, Osteoporosis (DURN) > Clinic of Nephrology and Hypertension 04 Faculty of Medicine > Pre-clinic Human Medicine > BioMedical Research (DBMR) > Unit Childrens Hospital > Forschungsgruppe Nephrologie / Hypertonie 09 Interdisciplinary Units > Microscopy Imaging Center (MIC) |
UniBE Contributor: |
Scherler, Laeticia Irène, Verouti, Sofia, Ackermann, Daniel, Vogt, Bruno, Escher, Geneviève |
Subjects: |
600 Technology > 610 Medicine & health |
ISSN: |
2218-273X |
Publisher: |
MDPI |
Language: |
English |
Submitter: |
Pubmed Import |
Date Deposited: |
29 Aug 2022 14:28 |
Last Modified: |
05 Dec 2022 16:23 |
Publisher DOI: |
10.3390/biom12081147 |
PubMed ID: |
36009040 |
Uncontrolled Keywords: |
atherosclerosis cholesterol efflux chronic kidney disease reverse cholesterol transport tibia |
BORIS DOI: |
10.48350/172427 |
URI: |
https://boris.unibe.ch/id/eprint/172427 |
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