Objective: CER-001 is an HDL mimetic that has been tested in different pathological conditions, but never with LCAT deficiency. This study was designed to investigate whether the absence of LCAT affects the catabolic fate of CER-001, and to evaluate the effects of CER-001 on kidney disease associated with LCAT deficiency. 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: Treatment with CER-001 ameliorates the dyslipidemia typically associated with LCAT deficiency and more importantly limits renal damage in a mouse model of renal disease in LCAT deficiency. The present results provide a rationale for using CER-001 in FLD patients.
CER-001 ameliorates lipid profile and kidney disease in a mouse model of familial LCAT deficiency / A. Ossoli, A. Strazzella, D. Rottoli, C. Zanchi, M. Locatelli, C. Zoja, S. Simonelli, F. Veglia, R. Barbaras, C. Tupin, J.-. Dasseux, L. Calabresi. - In: METABOLISM, CLINICAL AND EXPERIMENTAL. - ISSN 0026-0495. - 116(2021 Mar).
|Titolo:||CER-001 ameliorates lipid profile and kidney disease in a mouse model of familial LCAT deficiency|
OSSOLI, ALICE FEDERICA (Primo)
STRAZZELLA, ARIANNA (Secondo)
CALABRESI, LAURA (Ultimo) (Corresponding)
|Parole Chiave:||CER-001; Lecithin cholesterol acyltransferase deficiency; Lipids|
|Settore Scientifico Disciplinare:||Settore BIO/14 - Farmacologia|
|Data di pubblicazione:||mar-2021|
|Digital Object Identifier (DOI):||http://dx.doi.org/10.1016/j.metabol.2020.154464|
|Appare nelle tipologie:||01 - Articolo su periodico|