RT Dissertation/Thesis
T1 Coenzyme Q10 deficiency in familial hypercholesterolemia
A1 Suárez Rivero, Juan Miguel
K1 Biología celular
K1 Lípidos
K1 Coenzima Q10
AB Familial Hypercholesterolemia (FH) is an autosomal co-dominant genetic disorder characterized by elevated low-density lipoprotein (LDL) cholesterol levels and increased risk for premature cardiovascular disease. Here, we examined FH pathophysiology in skin fibroblasts derived from FH patients harboring heterozygous mutations in the LDL-receptor.Fibroblasts from FH patients showed a reduced LDL-uptake associated with increased intracellular cholesterol levels and coenzyme Q10 (CoQ10) deficiency, suggesting dysregulation of the mevalonate pathway. Secondary CoQ10 deficiency was associated with mitochondrial depolarization and mitophagy activation in FH fibroblasts. Persistent mitophagy altered autophagy flux and induced inflammasome activation accompanied by increased production of cytokines by mutant cells. All the pathological alterations in FH fibroblasts were also reproduced in a human endothelial cell line by LDL-receptor gene silencing.Both increased intracellular cholesterol and mitochondrial dysfunction in FH fibroblasts were partially restored by CoQ10 supplementation. Dysregulated mevalonate pathway in FH, including increased expression of cholesterogenic enzymes and decreased expression of CoQ10 biosynthetic enzymes, was also corrected by CoQ10 treatment.Reduced CoQ10 content and mitochondrial dysfunction may play an important role in the pathophysiology of early atherosclerosis in FH. The diagnosis of CoQ10 deficiency and mitochondrial impairment in FH patients may also be important to establish early treatment with CoQ10.
YR 2019
FD 2019
LK http://hdl.handle.net/10433/7171
UL http://hdl.handle.net/10433/7171
LA en
NO Programa de Doctorado en Biotecnología, Ingeniería y Tecnología Química
NO Línea de Investigación: Biología Celular, Molecular e Ingeniería Genética
NO Clave Programa: DBI
NO Código Línea: 8
NO Universidad Pablo de Olavide de Sevilla. Departamento de Fisiología, Anatomía y Biología Celular
DS RIO
RD May 6, 2026