Reverse Cholesterol Transport Dysfunction Is a Feature of Familial Hypercholesterolemia

Escolà‐Gil, Joan Carles; Rotllan, Noemí; Julve, Josep; Blanco‐Vaca, Francisco

doi:10.1007/s11883-021-00928-1

Cited by 11 publications

(11 citation statements)

References 60 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This finding stemmed from a study on ischemia-reperfusion injury in pigs, in which the beneficial vascular effects of HDL were abolished by hypercholesterolemia [42]. Notable evidence points to an altered macrophage-specific RCT in HeHF [43] (Figure 4). An impaired RCT, specifically related to the HDL2 subclass, with an inverse relationship between HDL efflux capacity and the development of atherosclerosis has been described in homozygous and HeFH patients [30].…”

Section: Defective Reverse Cholesterol Transport (Rct)mentioning

confidence: 99%

Familial Hypercholesterolemia: Do HDL Play a Role?

2021

View full text Add to dashboard Cite

Cardiovascular disease (CVD) in heterozygous familial hypercholesterolemia (HeFH), the most frequent monogenic disorder of human metabolism, is largely driven by low-density lipoprotein (LDL) cholesterol concentrations. Since the CVD rate differs considerably in this population, beyond the lifetime LDL cholesterol vascular accumulation, other classical risk factors are involved in the high cardiovascular risk of HeFH. Among other lipoprotein disturbances, alterations in the phenotype and functionality of high-density lipoproteins (HDL) have been described in HeFH patients, contributing to the presence and severity of CVD. In fact, HDL are the first defensive barrier against the burden of high LDL cholesterol levels owing to their contribution to reverse cholesterol transport as well as their antioxidant and anti-inflammatory properties, among others. In this context, the present narrative review aimed to focus on quantitative and qualitative abnormalities in HDL particles in HeFH, encompassing metabolic, genetic and epigenetic aspects.

show abstract

Section: Defective Reverse Cholesterol Transport (Rct)mentioning

confidence: 99%

Familial Hypercholesterolemia: Do HDL Play a Role?

2021

View full text Add to dashboard Cite

show abstract

“…It was reported that altered HDL remodeling and composition was associated with low HDL-C levels and dysfunctional RCT [ 39 ]. Despite an impaired CEC% in FH patients, HDL-C showed no statistical differences between the groups in the present study.…”

Section: Discussionmentioning

confidence: 99%

Capacity of HDL to Efflux Cellular Cholesterol from Lipid-Loaded Macrophages Is Reduced in Patients with Familial Hypercholesterolemia

et al. 2023

View full text Add to dashboard Cite

This study aimed to evaluate the high-density lipoprotein (HDL) capacity to efflux cellular cholesterol from lipid-loaded macrophages to find a reliable and low-cost biomarker with the purpose of better evaluating the risk of premature cardiovascular (CV) events in FH patients. This case-controlled study comprised 16 homozygous (HOFH) and 18 heterozygous (HEFH) FH patients, as well as 20 healthy subjects recruited as controls. Two main subfractions of HDL (HDL2 (d = 1.063–1.125 g/mL) and HDL3 (d = 1.125–1.210 g/mL)) were isolated from the patients’ serum samples using sequential ultracentrifugation. After compositional characterization, the capacity of HDL to efflux cholesterol (CEC%) from lipid-laden macrophages was measured. The HDL2 and HDL3 subfractions showed some differences in lipid and protein composition between the studied groups. In addition, both HDL subfractions (p < 0.001) revealed significantly reduced CEC% in HOFH patients (HDL2: 2.5 ± 0.1 and HDL3: 3.2 ± 0.2) in comparison with the HEFH (HDL2: 3.2 ± 0.1% and HDL3: 4.1 ± 0.2%) and healthy (HDL2: 3.3 ± 0.2% and HDL3: 4.5 ± 0.3%) subjects. Additionally, multinomial logistic regression results indicated that the CEC% of both HDL2 (OR: 0.091; 95% CI: 0.018–0.452, p < 0.01) and HDL3 (OR: 0.118; 95% CI: 0.035–0.399, p < 0.01) subfractions are strongly and inversely associated with the homozygous form of FH. A decreased capacity of HDL particles to efflux cholesterol from macrophages might identify homozygous FH patients who are at elevated risk for premature CVDs. Prospective studies with a large sample size are warranted to evaluate this hypothesis.

show abstract

“…First, given the fact that APOE4 carriers are known to be at a higher risk for the earlier onset of dementia [ 30 , 31 ], it is possible that the APOE3E4 carriers have higher HDL CEC as a positive compensatory response to a poorer efflux capacity over the entire lifetime. Second, APOE3E4 AD patients had a lower prevalence of metabolic disease (diabetes or hypercholesterolemia), which is known to be linked with poorer HDL function [ 32 , 33 ]. Third, we observed that APOE3E4 AD patients have more small HDL particles, and because we standardized the quantity of HDL used in the efflux experiment based on the HDL protein content, it is likely that a higher number of total HDL particles was applied to the assay compared to controls.…”

Section: Discussionmentioning

confidence: 99%

High-Density Lipoprotein Changes in Alzheimer’s Disease Are APOE Genotype-Specific

et al. 2022

View full text Add to dashboard Cite

High-density lipoproteins (HDL) play a critical role in cholesterol homeostasis. Apolipoprotein E (APOE), particularly the E4 allele, is a significant risk factor for Alzheimer’s disease but is also a key HDL-associated protein involved in lipid transport in both the periphery and central nervous systems. The objective was to determine the influence of the APOE genotype on HDL function and size in the context of Alzheimer’s disease. HDL from 194 participants (non-demented controls, mild cognitive impairment, and Alzheimer’s disease dementia) were isolated from the plasma. The HDL cholesterol efflux capacity (CEC), lecithin-cholesterol acyltransferase (LCAT) activity, and particle diameter were measured. Neuropsychological test scores, clinical dementia rating, and magnetic resonance imaging scores were used to determine if cognition is associated with HDL function and size. HDL CEC and LCAT activity were reduced in APOE3E4 carriers compared to APOE3E3 carriers, regardless of diagnosis. In APOE3E3 carriers, CEC and LCAT activity were lower in patients. In APOE3E4 patients, the average particle size was lower. HDL LCAT activity and particle size were positively correlated with the neuropsychological scores and negatively correlated with the clinical dementia rating. We provide evidence for the first time of APOE genotype-specific alterations in HDL particles in Alzheimer’s disease and an association between HDL function, size, and cognitive function.

show abstract

Reverse Cholesterol Transport Dysfunction Is a Feature of Familial Hypercholesterolemia

Cited by 11 publications

References 60 publications

Familial Hypercholesterolemia: Do HDL Play a Role?

Familial Hypercholesterolemia: Do HDL Play a Role?

Capacity of HDL to Efflux Cellular Cholesterol from Lipid-Loaded Macrophages Is Reduced in Patients with Familial Hypercholesterolemia

High-Density Lipoprotein Changes in Alzheimer’s Disease Are APOE Genotype-Specific

Contact Info

Product

Resources

About