Familial Hypercholesterolemia: Do HDL Play a Role?

Pedro‐Botet, Juan; Climent, Elisenda; Benaiges, David

doi:10.3390/biomedicines9070810

Cited by 16 publications

(13 citation statements)

References 85 publications

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“…In addition, HDL compositional changes in terms of protein and lipid cargo may also be hypothesized [ 42 ]. For instance, elevated sphingomyelin (SM) and saturated fatty acid content, as well as an increase in cholesterol esters and triglyceride content, was observed in HDL 3 particles isolated from FH patients [ 43 ].…”

Section: Discussionmentioning

confidence: 99%

HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma

Adorni

Biolo

Zimetti

et al. 2022

IJMS

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Achilles tendon xanthoma (ATX) formation involves macrophage cholesterol accumulation within the tendon, similar to that occurring in atheroma. Macrophage cholesterol homeostasis depends on serum lipoprotein functions, namely the high-density lipoprotein (HDL) capacity to promote cell cholesterol efflux (cholesterol efflux capacity, CEC) and the serum cholesterol loading capacity (CLC). We explored the HDL-CEC and serum CLC, comparing 16 FH patients with ATX to 29 FH patients without ATX. HDL-CEC through the main efflux mechanisms mediated by the transporters ATP binding cassette G1 (ABCG1) and A1 (ABCA1) and the aqueous diffusion (AD) process was determined by a cell-based radioisotopic technique and serum CLC fluorimetrically. Between the two groups, no significant differences were found in terms of plasma lipid profile. A trend toward reduction of cholesterol efflux via AD and a significant increase in ABCA1-mediated HDL-CEC (+18.6%) was observed in ATX compared to no ATX patients. In ATX-presenting patients, ABCG1-mediated HDL-CEC was lower (−11%) and serum CLC was higher (+14%) compared to patients without ATX. Considering all the patients together, ABCG1 HDL-CEC and serum CLC correlated with ATX thickness inversely (p = 0.013) and directly (p < 0.0001), respectively. In conclusion, lipoprotein dysfunctions seem to be involved in ATX physiopathology and progression in FH patients.

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Section: Discussionmentioning

confidence: 99%

HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma

Adorni

Biolo

Zimetti

et al. 2022

IJMS

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“…This is probably related to the fact that, in subjects with FH, there is an increase in both synthesis and catabolism of HDL particles, but there may be an imbalance between both processes that varies depending on population-specific genetic or environmental factors. Increased apoA-1 catabolism due to increased cholesteryl ester transfer protein activity favours the generation of small HDL particles rich in triglycerides and apolipoprotein E [ 144 , 145 ]. Moreover, HDL particles in subjects with FH may show different functional abnormalities not detectable by measuring HDL-c alone.…”

Section: Coexistence Of Diabetes and Familial Hypercholesterolemia: C...mentioning

confidence: 99%

“…Moreover, HDL particles in subjects with FH may show different functional abnormalities not detectable by measuring HDL-c alone. This may include a defective ability to reverse cholesterol transport from macrophages and impaired anti-inflammatory and antioxidant capacity [ 144 , 145 ].…”

Section: Coexistence Of Diabetes and Familial Hypercholesterolemia: C...mentioning

confidence: 99%

Diabetes and Familial Hypercholesterolemia: Interplay between Lipid and Glucose Metabolism

et al. 2022

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Familial hypercholesterolemia (FH) is a genetic disease characterized by high low-density lipoprotein (LDL) cholesterol (LDL-c) concentrations that increase cardiovascular risk and cause premature death. The most frequent cause of the disease is a mutation in the LDL receptor (LDLR) gene. Diabetes is also associated with an increased risk of cardiovascular disease and mortality. People with FH seem to be protected from developing diabetes, whereas cholesterol-lowering treatments such as statins are associated with an increased risk of the disease. One of the hypotheses to explain this is based on the toxicity of LDL particles on insulin-secreting pancreatic β-cells, and their uptake by the latter, mediated by the LDLR. A healthy lifestyle and a relatively low body mass index in people with FH have also been proposed as explanations. Its association with superimposed diabetes modifies the phenotype of FH, both regarding the lipid profile and cardiovascular risk. However, findings regarding the association and interplay between these two diseases are conflicting. The present review summarizes the existing evidence and discusses knowledge gaps on the matter.

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“…Low HDL-C phenotype has been associated with a 37% relative increase in the CVD risk and was suggested to be a strong marker of preclinical carotid atherosclerosis in HeFH patients [ 16 ]. Moreover, HDL functions are often harmed in FH [ 17 ] due to additive changes in proteins, enzymes, lipids, and microRNA which lead to the loss of their atheroprotective properties [ 18 ].…”

Section: Coexisting Dyslipidemias With Fhmentioning

confidence: 99%

Clinical Aspects of Genetic and Non-Genetic Cardiovascular Risk Factors in Familial Hypercholesterolemia

Berta

Zsíros

Bodor

et al. 2022

Genes

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Familial hypercholesterolemia (FH) is the most common monogenic metabolic disorder characterized by considerably elevated low-density lipoprotein cholesterol (LDL-C) levels leading to enhanced atherogenesis, early cardiovascular disease (CVD), and premature death. However, the wide phenotypic heterogeneity in FH makes the cardiovascular risk prediction challenging in clinical practice to determine optimal therapeutic strategy. Beyond the lifetime LDL-C vascular accumulation, other genetic and non-genetic risk factors might exacerbate CVD development. Besides the most frequent variants of three genes (LDL-R, APOB, and PCSK9) in some proband variants of other genes implicated in lipid metabolism and atherogenesis are responsible for FH phenotype. Furthermore, non-genetic factors, including traditional cardiovascular risk factors, metabolic and endocrine disorders might also worsen risk profile. Although some were extensively studied previously, others, such as common endocrine disorders including thyroid disorders or polycystic ovary syndrome are not widely evaluated in FH. In this review, we summarize the most important genetic and non-genetic factors that might affect the risk prediction and therapeutic strategy in FH through the eyes of clinicians focusing on disorders that might not be in the center of FH research. The review highlights the complexity of FH care and the need of an interdisciplinary attitude to find the best therapeutic approach in FH patients.

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Familial Hypercholesterolemia: Do HDL Play a Role?

Cited by 16 publications

References 85 publications

HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma

HDL Cholesterol Efflux and Serum Cholesterol Loading Capacity Alterations Associate to Macrophage Cholesterol Accumulation in FH Patients with Achilles Tendon Xanthoma

Diabetes and Familial Hypercholesterolemia: Interplay between Lipid and Glucose Metabolism

Clinical Aspects of Genetic and Non-Genetic Cardiovascular Risk Factors in Familial Hypercholesterolemia

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