Abstract | OBJECTIVE: METHODS: Lcat-/- and wild-type mice received CER-001 (2.5, 5, 10 mg/kg) intravenously for 2 weeks. The plasma lipid/ lipoprotein profile and HDL subclasses were analyzed. In a second set of experiments, Lcat-/- mice were injected with LpX to induce renal disease and treated with CER-001 and then the plasma lipid profile, lipid accumulation in the kidney, albuminuria and glomerular podocyte markers were evaluated. RESULTS: In Lcat-/- mice a decrease in total cholesterol and triglycerides, and an increase in HDL-c was observed after CER-001 treatment. While in wild-type mice CER-001 entered the classical HDL remodeling pathway, in the absence of LCAT it disappeared from the plasma shortly after injection and ended up in the kidney. In a mouse model of renal disease in LCAT deficiency, treatment with CER-001 at 10 mg/kg for one month had beneficial effects not only on the lipid profile, but also on renal disease, by limiting albuminuria and podocyte dysfunction. CONCLUSIONS:
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Authors | Alice Ossoli, Arianna Strazzella, Daniela Rottoli, Cristina Zanchi, Monica Locatelli, Carlamaria Zoja, Sara Simonelli, Fabrizio Veglia, Ronald Barbaras, Cyrille Tupin, Jean-Louis Dasseux, Laura Calabresi |
Journal | Metabolism: clinical and experimental
(Metabolism)
Vol. 116
Pg. 154464
(03 2021)
ISSN: 1532-8600 [Electronic] United States |
PMID | 33309714
(Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
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Copyright | Copyright © 2020 Elsevier Inc. All rights reserved. |
Chemical References |
- Apolipoprotein A-I
- CER-001
- Lipids
- Phospholipids
- Recombinant Proteins
- Phosphatidylcholine-Sterol O-Acyltransferase
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Topics |
- Animals
- Apolipoprotein A-I
(pharmacology, therapeutic use)
- Cells, Cultured
- Disease Models, Animal
- Kidney Diseases
(drug therapy, genetics, pathology)
- Lecithin Cholesterol Acyltransferase Deficiency
(drug therapy, genetics, metabolism, pathology)
- Lipid Metabolism
(drug effects)
- Lipids
(blood)
- Mice
- Mice, Inbred C57BL
- Mice, Knockout
- Phosphatidylcholine-Sterol O-Acyltransferase
(genetics)
- Phospholipids
(pharmacology, therapeutic use)
- Podocytes
(drug effects, pathology, physiology)
- Recombinant Proteins
(pharmacology, therapeutic use)
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