Journal of clinical lipidology · 2026
Reduced LDL receptor expression and LDL uptake in lymphoblastoid cells from a patient with cholesteryl ester storage disease.
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Jan Maëlle, Lebel Marie-Nathalie, Bluteau Olivier, Carrié Alain, Perregaux Jean-François, Bekri Soumeya, Rabès Jean-Pierre, Gallo Antonio, Varret Mathilde
Аннотация
BACKGROUND: Lysosomal acid lipase deficiency (LAL-D) is characterized by severe dyslipidemia, including elevated low-density lipoprotein (LDL) cholesterol, despite activation of sterol-responsive pathways.
OBJECTIVE: We investigated whether altered receptor-mediated LDL catabolism may contribute to this phenotype.
METHODS: Epstein-Barr virus (EBV)-transformed lymphoblastoid cells from a patient with cholesteryl ester storage disease (CESD) homozygous for the LIPA Exon 8 Splice-Junction Mutation were compared with cells from heterozygous carriers, heterozygous familial hypercholesterolemia patients, and controls. LAL activity was measured using a fluorometric assay. LDL receptor (LDLR) surface expression and LDL internalization were assessed by flow cytometry.
RESULTS: CESD cells displayed markedly reduced LAL activity together with modest but significant reductions in LDLR surface expression and LDL internalization. Under low-serum conditions, LDLR gene expression was also significantly lower in CESD cells than in controls.
CONCLUSION: These findings suggest that impaired LDLR-mediated LDL uptake may contribute to dyslipidemia in LAL-D, alongside previously reported alterations in lipoprotein production. Confirmation in additional patients and disease-relevant cellular models is required.
OBJECTIVE: We investigated whether altered receptor-mediated LDL catabolism may contribute to this phenotype.
METHODS: Epstein-Barr virus (EBV)-transformed lymphoblastoid cells from a patient with cholesteryl ester storage disease (CESD) homozygous for the LIPA Exon 8 Splice-Junction Mutation were compared with cells from heterozygous carriers, heterozygous familial hypercholesterolemia patients, and controls. LAL activity was measured using a fluorometric assay. LDL receptor (LDLR) surface expression and LDL internalization were assessed by flow cytometry.
RESULTS: CESD cells displayed markedly reduced LAL activity together with modest but significant reductions in LDLR surface expression and LDL internalization. Under low-serum conditions, LDLR gene expression was also significantly lower in CESD cells than in controls.
CONCLUSION: These findings suggest that impaired LDLR-mediated LDL uptake may contribute to dyslipidemia in LAL-D, alongside previously reported alterations in lipoprotein production. Confirmation in additional patients and disease-relevant cellular models is required.