Joan Carles Escolà-Gil1,2,3, Noemí Rotllan4,5, Josep Julve4,5,6, Francisco Blanco-Vaca5,6,7. 1. Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain. jescola@santpau.cat. 2. CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Madrid, Spain. jescola@santpau.cat. 3. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain. jescola@santpau.cat. 4. Institut de Recerca de l'Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain. 5. CIBER de Diabetes y Enfermedades Metabólicas Asociadas, CIBERDEM, Madrid, Spain. 6. Departament de Bioquímica i Biologia Molecular, Universitat Autònoma de Barcelona, Barcelona, Spain. 7. Servei de Bioquímica, Hospital de la Santa Creu i Sant Pau, Institut d'Investigacions Biomèdiques (IIB) Sant Pau, Barcelona, Spain.
Abstract
PURPOSE OF REVIEW: We seek to establish whether high-density lipoprotein HDL metabolism and reverse cholesterol transport (RCT) impairment is an intrinsic feature of familial hypercholesterolemia (FH). RECENT FINDINGS: RCT from macrophages (m-RCT), a vascular cell type of major influence on atherosclerosis, is impaired in FH due to defective low-density lipoprotein receptor (LDLR) function via both the HDL- and LDL-mediated pathways. Potential mechanisms include impaired HDL metabolism, which is linked to increased LDL levels, as well as the increased transport of cellular unesterified cholesterol to LDL, which presents a defective catabolism. RCT dysfunction is consistently associated with mutation-positive FH linked to decreased HDL levels as well as impaired HDL remodeling and LDLR function. It remains to be explored whether these alterations are also present in less well-characterized forms of FH, such as cases with no identified mutations, and whether they are fully corrected by current standard treatments.
PURPOSE OF REVIEW: We seek to establish whether high-density lipoprotein HDL metabolism and reverse cholesterol transport (RCT) impairment is an intrinsic feature of familial hypercholesterolemia (FH). RECENT FINDINGS: RCT from macrophages (m-RCT), a vascular cell type of major influence on atherosclerosis, is impaired in FH due to defective low-density lipoprotein receptor (LDLR) function via both the HDL- and LDL-mediated pathways. Potential mechanisms include impaired HDL metabolism, which is linked to increased LDL levels, as well as the increased transport of cellular unesterified cholesterol to LDL, which presents a defective catabolism. RCT dysfunction is consistently associated with mutation-positive FH linked to decreased HDL levels as well as impaired HDL remodeling and LDLR function. It remains to be explored whether these alterations are also present in less well-characterized forms of FH, such as cases with no identified mutations, and whether they are fully corrected by current standard treatments.
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