NDLI: Lomitapide modifies high-density lipoprotein function in homozygous familial hypercholesterolaemia

Content Provider	Springer Nature : BioMed Central
Author	Hafiane, Anouar Ronca, Annalisa Incerti, Matteo Rossi, Alessandra Manfredini, Matteo Favari, Elda
Abstract	Background Lomitapide reduces plasma low-density lipoprotein cholesterol (LDL-C) and is approved for the treatment of homozygous familial hypercholesterolemia (HoFH). This study aims to determine the effect of lomitapide on HDL and cholesterol efflux in a cohort of patients with HoFH. Patients and methods Analysis included plasma samples from 17 HoFH patients enrolled in the lomitapide phase 3 Aegerion clinical study (NCT00730236). Samples taken at baseline (pre-lomitapide) and weeks 56 and 66 (assumed steady-state on lomitapide) were analyzed for HDL-C levels and cholesterol efflux capacity (CEC) pathways via ABCA1, ABCG1, and SR–BI cholesterol uptake. Results Treatment with lomitapide is associated with a statistically significant decrease of both LDL-C and apo B when compared to baseline levels, p < 0.01. However, the reduction of Lp(a) appears only at a higher dose when compared to baseline (− 27% against values around − 55% for LDL-C and apo B). HDL-C shows a small 4.2% increase between the baseline and the treatment with a high dosage of lomitapide, while apo A–I displays an opposite small 3% decrease. Total efflux and ABCA1 mediated CEC decreased especially at higher dosage of lomitapide, with marked dose-dependent increase of SR–BI cholesterol uptake (+ 21.4% and + 64.3%, respectively, at a low and high dosages of lomitapide). However, ABCG1 did not change consistently. Conclusions Our report raises the hypothesis that lomitapide promotes lipidation of HDL particles independently of ABCA1 and ABCG1 through a process involving SR–BI pathway. This effect impairs the total efflux process suggesting that lomitapide drives the reverse cholesterol transport through SR–BI receptors in HoFH patients.
Related Links	https://eurjmedres.biomedcentral.com/counter/pdf/10.1186/s40001-025-02439-0.pdf
Ending Page	9
Page Count	9
Starting Page	1
File Format	HTM / HTML
DOI	10.1186/s40001-025-02439-0
Journal	European Journal of Medical Research
Issue Number	1
Volume Number	30
Language	English
Publisher	BioMed Central
Publisher Date	2025-04-11
Access Restriction	Open
Subject Keyword	Medicine Public Health Infectious Diseases Internal Medicine Surgery Oncology Biomedicine Apo B Cholesterol efflux capacity HDL cholesterol Homozygous familial hypercholesterolaemia Lomitapide LDL cholesterol Medicine/Public Health
Content Type	Text
Resource Type	Article
Subject	Medicine
Journal Impact Factor	2.8/2023
5-Year Journal Impact Factor	2.9/2023

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