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High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in...
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High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Chemical Biology".

Deadline for manuscript submissions: closed (31 August 2020) | Viewed by 54228

Special Issue Editor

Dr. Anand K. Rohatgi

E-Mail Website
Guest Editor
Department of Internal Medicine, University of Texas Southwestern Medical Center, Dallas, TX 75390-8830, USA
Interests: elucidating the role of HDL and reverse cholesterol transport in atheroprotection
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Although high-density lipoprotein (HDL) cholesterol levels continue to be included in cardiovascular risk assessment tools, findings from genetic studies and various pharmacologic interventions have called into question the causal role of HDL cholesterol in atherosclerotic heart disease and the suitability of HDL cholesterol as a treatment target. Recent studies have illuminated the dynamic and complex HDL metabolic pathways defined by lipid transport out of the cell, reverse cholesterol transport (RCT), but directly linked to a myriad of other vascular and non-vascular functions.  It has become increasingly clear that HDL metabolism has direct relevance to a number of pathophysiologic processes.

I am pleased to announce this Special Issue, which aims to address how HDL and RCT may impact fundamental biologic processes as well as contribute to pathophysiology across a spectrum of human diseases. A major focus of this issue is to structure our current understanding of HDL and RCT by disease process and to emphasize both the fundamental basic science as well as the relevance to human disease.

Dr. Anand K. Rohatgi
Guest Editor

Keywords

  • high-density lipoprotein (HDL)
  • reverse cholesterol transport
  • atherosclerosis
  • cancer
  • renal disease
  • dementia
  • vascular disease
  • therapy
  • lifestyle
  • macular degeneration

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Published Papers (12 papers)

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Research

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19 pages, 3096 KiB  
Article
Subcutaneous Administration of Apolipoprotein J-Derived Mimetic Peptide d-[113–122]apoJ Improves LDL and HDL Function and Prevents Atherosclerosis in LDLR-KO Mice
by Andrea Rivas-Urbina, Anna Rull, Joile Aldana-Ramos, David Santos, Nuria Puig, Nuria Farre-Cabrerizo, Sonia Benitez, Antonio Perez, David de Gonzalo-Calvo, Joan Carles Escola-Gil, Josep Julve, Jordi Ordoñez-Llanos and Jose Luis Sanchez-Quesada
Biomolecules 2020, 10(6), 829; https://doi.org/10.3390/biom10060829 - 29 May 2020
Cited by 19 | Viewed by 3690
Abstract
Mimetic peptides are potential therapeutic agents for atherosclerosis. d-[113–122]apolipoprotein (apo) J (d-[113–122]apoJ) is a 10-residue peptide that is predicted to form a class G* amphipathic helix 6 from apoJ; it shows anti-inflammatory and anti-atherogenic properties. In the present study, we [...] Read more.
Mimetic peptides are potential therapeutic agents for atherosclerosis. d-[113–122]apolipoprotein (apo) J (d-[113–122]apoJ) is a 10-residue peptide that is predicted to form a class G* amphipathic helix 6 from apoJ; it shows anti-inflammatory and anti-atherogenic properties. In the present study, we analyzed the effect of d-[113–122]apoJ in low-density lipoprotein receptor knockout mice(LDLR-KO) on the development of atherosclerosis and lipoprotein function. Fifteen-week-old female LDLR-KO mice fed an atherogenic Western-type diet were treated for eight weeks with d-[113–122]apoJ peptide, a scrambled peptide, or vehicle. Peptides were administered subcutaneously three days per week (200 µg in 100 µL of saline). After euthanasia, blood and hearts were collected and the aortic arch was analyzed for the presence of atherosclerotic lesions. Lipoproteins were isolated and their composition and functionality were studied. The extent of atherosclerotic lesions was 43% lower with d-[113–122]apoJ treatment than with the vehicle or scramble. The lipid profile was similar between groups, but the high-density lipoprotein (HDL) of d-[113–122]apoJ-treated mice had a higher antioxidant capacity and increased ability to promote cholesterol efflux than the control group. In addition, low-density lipoprotein (LDL) from d-[113–122]apoJ-treated mice was more resistant to induced aggregation and presented lower electronegativity than in mice treated with d-[113–122]apoJ. Our results demonstrate that the d-[113–122]apoJ peptide prevents the extent of atherosclerotic lesions, which could be partially explained by the improvement of lipoprotein functionality. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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18 pages, 2619 KiB  
Article
Reduced Reverse Cholesterol Transport Efficacy in Healthy Men with Undesirable Postprandial Triglyceride Response
by Alexandre Motte, Julie Gall, Joe-Elie Salem, Eric Dasque, Martine Lebot, Eric Frisdal, Sophie Galier, Elise F. Villard, Elodie Bouaziz-Amar, Jean-Marc Lacorte, Beny Charbit, Wilfried Le Goff, Philippe Lesnik and Maryse Guerin
Biomolecules 2020, 10(5), 810; https://doi.org/10.3390/biom10050810 - 25 May 2020
Cited by 6 | Viewed by 3944
Abstract
Elevation of nonfasting triglyceride (TG) levels above 1.8 g/L (2 mmol/L) is associated with increased risk of cardiovascular diseases. Exacerbated postprandial hypertriglyceridemia (PP–HTG) and metabolic context both modulate the overall efficacy of the reverse cholesterol transport (RCT) pathway, but the specific contribution of [...] Read more.
Elevation of nonfasting triglyceride (TG) levels above 1.8 g/L (2 mmol/L) is associated with increased risk of cardiovascular diseases. Exacerbated postprandial hypertriglyceridemia (PP–HTG) and metabolic context both modulate the overall efficacy of the reverse cholesterol transport (RCT) pathway, but the specific contribution of exaggerated PP–HTG on RCT efficacy remains indeterminate. Healthy male volunteers (n = 78) exhibiting no clinical features of metabolic disorders underwent a postprandial exploration following consumption of a typical Western meal providing 1200 kcal. Subjects were stratified according to maximal nonfasting TG levels reached after ingestion of the test meal into subjects with a desirable PP–TG response (GLow, TG < 1.8 g/L, n = 47) and subjects with an undesirable PP–TG response (GHigh, TG > 1.8 g/L, n = 31). The impact of the degree of PP–TG response on major steps of RCT pathway, including cholesterol efflux from human macrophages, cholesteryl ester transfer protein (CETP) activity, and hepatic high-density lipoprotein (HDL)-cholesteryl ester (CE) selective uptake, was evaluated. Cholesterol efflux from human macrophages was not significantly affected by the degree of the PP–TG response. Postprandial increase in CETP-mediated CE transfer from HDL to triglyceride-rich lipoprotein particles, and more specifically to chylomicrons, was enhanced in GHigh vs. GLow. The hepatic HDL-CE delivery was reduced in subjects from GHigh in comparison with those from GLow. Undesirable PP–TG response induces an overall reduction in RCT efficacy that contributes to the onset elevation of both fasting and nonfasting TG levels and to the development of cardiometabolic diseases. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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10 pages, 715 KiB  
Article
Macrophage Cholesterol Efflux Downregulation Is Not Associated with Abdominal Aortic Aneurysm (AAA) Progression
by Marina Canyelles, Mireia Tondo, Jes S. Lindholt, David Santos, Irati Fernández-Alonso, David de Gonzalo-Calvo, Luis Miguel Blanco-Colio, Joan Carles Escolà-Gil, José Luís Martín-Ventura and Francisco Blanco-Vaca
Biomolecules 2020, 10(4), 662; https://doi.org/10.3390/biom10040662 - 24 Apr 2020
Cited by 2 | Viewed by 3125
Abstract
Recent studies have raised the possibility of a role for lipoproteins, including high-density lipoprotein cholesterol (HDLc), in abdominal aortic aneurysm (AAA). The study was conducted in plasmas from 39 large size AAA patients (aortic diameter > 50 mm), 81 small/medium size AAA patients [...] Read more.
Recent studies have raised the possibility of a role for lipoproteins, including high-density lipoprotein cholesterol (HDLc), in abdominal aortic aneurysm (AAA). The study was conducted in plasmas from 39 large size AAA patients (aortic diameter > 50 mm), 81 small/medium size AAA patients (aortic diameter between 30 and 50 mm) and 38 control subjects (aortic diameter < 30 mm). We evaluated the potential of HDL-mediated macrophage cholesterol efflux (MCE) to predict AAA growth and/or the need for surgery. MCE was impaired in the large aortic diameter AAA group as compared with that in the small/medium size AAA group and the control group. However, no significant difference in HDL-mediated MCE capacity was observed in 3 different progression subgroups (classified according to growth rate < 1 mm per year, between 1 and 5 mm per year or >5 mm per year) in patients with small/medium size AAA. Moreover, no correlation was found between MCE capacity and the aneurysm growth rate. A multivariate Cox regression analysis revealed a significant association between lower MCE capacity with the need for surgery in all AAA patients. Nevertheless, the significance was lost when only small/medium size AAA patients were included. Our results suggest that MCE, a major HDL functional activity, is not involved in AAA progression. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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13 pages, 4093 KiB  
Article
Bariatric Surgery Improves HDL Function Examined by ApoA1 Exchange Rate and Cholesterol Efflux Capacity in Patients with Obesity and Type 2 Diabetes
by Shuhui Wang Lorkowski, Gregory Brubaker, Daniel M. Rotroff, Sangeeta R. Kashyap, Deepak L. Bhatt, Steven E. Nissen, Philip R. Schauer, Ali Aminian and Jonathan D. Smith
Biomolecules 2020, 10(4), 551; https://doi.org/10.3390/biom10040551 - 4 Apr 2020
Cited by 34 | Viewed by 4414
Abstract
Bariatric surgery improves glycemic control better than medical therapy; however, the effect of bariatric surgery on HDL function is not well characterized. Serum samples were available at baseline, 1-, and 5-years post procedures, for 90 patients with obesity and type 2 diabetes who [...] Read more.
Bariatric surgery improves glycemic control better than medical therapy; however, the effect of bariatric surgery on HDL function is not well characterized. Serum samples were available at baseline, 1-, and 5-years post procedures, for 90 patients with obesity and type 2 diabetes who were randomized to intensive medical therapy (n = 20), Roux-en-Y gastric bypass (RYGB, n = 37), or sleeve gastrectomy (SG, n = 33) as part of the STAMPEDE clinical trial. We examined serum HDL function by two independent assays, apolipoprotein A-1 exchange rate (AER) and cholesterol efflux capacity (CEC). Compared with baseline, AER was significantly higher at 5 years for participants in all treatment groups, but only increased significantly at 1 year in the RYGB and SG groups. CEC was divided into ABCA1-dependent and independent fractions, and the later was correlated with AER. ABCA1-independent CEC increased significantly only at 5 years in both surgical groups, but did not significantly change in the medical therapy group. There was no significant change in ABCA1-dependent CEC in any group. The increase in AER, but not ABCA1-independent CEC, was correlated with the reduction in body mass index and glycated hemoglobin levels among all subjects at 5 years, indicating that AER as a measure of HDL function would be a better reflection of therapy versus CEC. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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16 pages, 846 KiB  
Article
Temporal Dynamics of High-Density Lipoprotein Proteome in Diet-Controlled Subjects with Type 2 Diabetes
by Karim G. Kheniser, Abdullah Osme, Chunki Kim, Serguei Ilchenko, Takhar Kasumov and Sangeeta R. Kashyap
Biomolecules 2020, 10(4), 520; https://doi.org/10.3390/biom10040520 - 30 Mar 2020
Cited by 12 | Viewed by 3275
Abstract
We examined the effect of mild hyperglycemia on high-density lipoprotein (HDL) metabolism and kinetics in diet-controlled subjects with type 2 diabetes (T2D). 2H2O-labeling coupled with mass spectrometry was applied to quantify HDL cholesterol turnover and HDL proteome dynamics in subjects [...] Read more.
We examined the effect of mild hyperglycemia on high-density lipoprotein (HDL) metabolism and kinetics in diet-controlled subjects with type 2 diabetes (T2D). 2H2O-labeling coupled with mass spectrometry was applied to quantify HDL cholesterol turnover and HDL proteome dynamics in subjects with T2D (n = 9) and age- and BMI-matched healthy controls (n = 8). The activities of lecithin–cholesterol acyltransferase (LCAT), cholesterol ester transfer protein (CETP), and the proinflammatory index of HDL were quantified. Plasma adiponectin levels were reduced in subjects with T2D, which was directly associated with suppressed ABCA1-dependent cholesterol efflux capacity of HDL. The fractional catabolic rates of HDL cholesterol, apolipoprotein A-II (ApoA-II), ApoJ, ApoA-IV, transthyretin, complement C3, and vitamin D-binding protein (all p < 0.05) were increased in subjects with T2D. Despite increased HDL flux of acute-phase HDL proteins, there was no change in the proinflammatory index of HDL. Although LCAT and CETP activities were not affected in subjects with T2D, LCAT was inversely associated with blood glucose and CETP was inversely associated with plasma adiponectin. The degradation rates of ApoA-II and ApoA-IV were correlated with hemoglobin A1c. In conclusion, there were in vivo impairments in HDL proteome dynamics and HDL metabolism in diet-controlled patients with T2D. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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14 pages, 517 KiB  
Article
High-Density Lipoprotein Particles and Their Relationship to Posttransplantation Diabetes Mellitus in Renal Transplant Recipients
by Sara Sokooti, Tamas Szili-Torok, Jose L. Flores-Guerrero, Maryse C. J. Osté, António W. Gomes-Neto, Jenny E. Kootstra-Ros, Hiddo J.L. Heerspink, Margery A. Connelly, Stephan J. L. Bakker and Robin P. F. Dullaart
Biomolecules 2020, 10(3), 481; https://doi.org/10.3390/biom10030481 - 21 Mar 2020
Cited by 9 | Viewed by 3766
Abstract
High concentrations of high-density lipoprotein (HDL) cholesterol are likely associated with a lower risk of posttransplantation diabetes mellitus (PTDM). However, HDL particles vary in size and density with yet unestablished associations with PTDM risk. The aim of our study was to determine the [...] Read more.
High concentrations of high-density lipoprotein (HDL) cholesterol are likely associated with a lower risk of posttransplantation diabetes mellitus (PTDM). However, HDL particles vary in size and density with yet unestablished associations with PTDM risk. The aim of our study was to determine the association between different HDL particles and development of PTDM in renal transplant recipients (RTRs). We included 351 stable outpatient adult RTRs without diabetes at baseline evaluation. HDL particle characteristics and size were measured by nuclear magnetic resonance (NMR) spectroscopy. During 5.2 (IQR, 4.1‒5.8) years of follow-up, 39 (11%) RTRs developed PTDM. In multivariable Cox regression analysis, levels of HDL cholesterol (hazard ratio [HR] 0.61, 95% confidence interval [CI] 0.40–0.94 per 1SD increase; p = 0.024) and of large HDL particles (HR 0.68, 95% CI 0.50–0.93 per log 1SD increase; p = 0.017), as well as larger HDL size (HR 0.58, 95% CI 0.36–0.93 per 1SD increase; p = 0.025) were inversely associated with PTDM development, independently of relevant covariates including, age, sex, body mass index, medication use, transplantation-specific parameters, blood pressure, triglycerides, and glucose. In conclusion, higher concentrations of HDL cholesterol and of large HDL particles and greater HDL size were associated with a lower risk of PTDM development in RTRs, independently of established risk factors for PTDM development. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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24 pages, 3271 KiB  
Article
Protein Backbone and Average Particle Dynamics in Reconstituted Discoidal and Spherical HDL Probed by Hydrogen Deuterium Exchange and Elastic Incoherent Neutron Scattering
by Valentin Gogonea, Judith Peters, Gary S. Gerstenecker, Celalettin Topbas, Liming Hou, Jérôme Combet, Joseph A. DiDonato, Jonathan D. Smith, Kerry-Anne Rye and Stanley L. Hazen
Biomolecules 2020, 10(1), 121; https://doi.org/10.3390/biom10010121 - 10 Jan 2020
Cited by 2 | Viewed by 3669
Abstract
Lipoproteins are supramolecular assemblies of proteins and lipids with dynamic characteristics critically linked to their biological functions as plasma lipid transporters and lipid exchangers. Among them, spherical high-density lipoproteins are the most abundant forms of high-density lipoprotein (HDL) in human plasma, active participants [...] Read more.
Lipoproteins are supramolecular assemblies of proteins and lipids with dynamic characteristics critically linked to their biological functions as plasma lipid transporters and lipid exchangers. Among them, spherical high-density lipoproteins are the most abundant forms of high-density lipoprotein (HDL) in human plasma, active participants in reverse cholesterol transport, and associated with reduced development of atherosclerosis. Here, we employed elastic incoherent neutron scattering (EINS) and hydrogen-deuterium exchange mass spectrometry (HDX-MS) to determine the average particle dynamics and protein backbone local mobility of physiologically competent discoidal and spherical HDL particles reconstituted with human apolipoprotein A-I (apoA-I). Our EINS measurements indicated that discoidal HDL was more dynamic than spherical HDL at ambient temperatures, in agreement with their lipid-protein composition. Combining small-angle neutron scattering (SANS) with contrast variation and MS cross-linking, we showed earlier that the most likely organization of the three apolipoprotein A-I (apoA-I) chains in spherical HDL is a combination of a hairpin monomer and a helical antiparallel dimer. Here, we corroborated those findings with kinetic studies, employing hydrogen-deuterium exchange mass spectrometry (HDX-MS). Many overlapping apoA-I digested peptides exhibited bimodal HDX kinetics behavior, suggesting that apoA-I regions with the same amino acid composition located on different apoA-I chains had different conformations and/or interaction environments. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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Review

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23 pages, 1442 KiB  
Review
Current Understanding of the Relationship of HDL Composition, Structure and Function to Their Cardioprotective Properties in Chronic Kidney Disease
by Gunther Marsche, Gunnar H. Heine, Julia T. Stadler and Michael Holzer
Biomolecules 2020, 10(9), 1348; https://doi.org/10.3390/biom10091348 - 21 Sep 2020
Cited by 30 | Viewed by 4759
Abstract
In the general population, the ability of high-density lipoproteins (HDLs) to promote cholesterol efflux is a predictor of cardiovascular events, independently of HDL cholesterol levels. Although patients with chronic kidney disease (CKD) have a high burden of cardiovascular morbidity and mortality, neither serum [...] Read more.
In the general population, the ability of high-density lipoproteins (HDLs) to promote cholesterol efflux is a predictor of cardiovascular events, independently of HDL cholesterol levels. Although patients with chronic kidney disease (CKD) have a high burden of cardiovascular morbidity and mortality, neither serum levels of HDL cholesterol, nor cholesterol efflux capacity associate with cardiovascular events. Important for the following discussion on the role of HDL in CKD is the notion that traditional atherosclerotic cardiovascular risk factors only partially account for this increased incidence of cardiovascular disease in CKD. As a potential explanation, across the spectrum of cardiovascular disease, the relative contribution of atherosclerotic cardiovascular disease becomes less important with advanced CKD. Impaired renal function directly affects the metabolism, composition and functionality of HDL particles. HDLs themselves are a heterogeneous population of particles with distinct sizes and protein composition, all of them affecting the functionality of HDL. Therefore, a more specific approach investigating the functional and compositional features of HDL subclasses might be a valuable strategy to decipher the potential link between HDL, cardiovascular disease and CKD. This review summarizes the current understanding of the relationship of HDL composition, metabolism and function to their cardio-protective properties in CKD, with a focus on CKD-induced changes in the HDL proteome and reverse cholesterol transport capacity. We also will highlight the gaps in the current knowledge regarding important aspects of HDL biology. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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28 pages, 1112 KiB  
Review
The Role of HDL and HDL Mimetic Peptides as Potential Therapeutics for Alzheimer’s Disease
by Dustin Chernick, Rui Zhong and Ling Li
Biomolecules 2020, 10(9), 1276; https://doi.org/10.3390/biom10091276 - 4 Sep 2020
Cited by 19 | Viewed by 5603
Abstract
The role of high-density lipoproteins (HDL) in the cardiovascular system has been extensively studied and the cardioprotective effects of HDL are well established. As HDL particles are formed both in the systemic circulation and in the central nervous system, the role of HDL [...] Read more.
The role of high-density lipoproteins (HDL) in the cardiovascular system has been extensively studied and the cardioprotective effects of HDL are well established. As HDL particles are formed both in the systemic circulation and in the central nervous system, the role of HDL and its associated apolipoproteins in the brain has attracted much research interest in recent years. Alzheimer’s disease (AD) is the most prevalent neurodegenerative disorder and the leading cause of dementia worldwide, for which there currently exists no approved disease modifying treatment. Multiple lines of evidence, including a number of large-scale human clinical studies, have shown a robust connection between HDL levels and AD. Low levels of HDL are associated with increased risk and severity of AD, whereas high levels of HDL are correlated with superior cognitive function. Although the mechanisms underlying the protective effects of HDL in the brain are not fully understood, many of the functions of HDL, including reverse lipid/cholesterol transport, anti-inflammation/immune modulation, anti-oxidation, microvessel endothelial protection, and proteopathy modification, are thought to be critical for its beneficial effects. This review describes the current evidence for the role of HDL in AD and the potential of using small peptides mimicking HDL or its associated apolipoproteins (HDL-mimetic peptides) as therapeutics to treat AD. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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16 pages, 1860 KiB  
Review
The Alcohol–High-Density Lipoprotein Athero-Protective Axis
by Corina Rosales, Baiba K. Gillard, Antonio M. Gotto, Jr. and Henry J. Pownall
Biomolecules 2020, 10(7), 987; https://doi.org/10.3390/biom10070987 - 1 Jul 2020
Cited by 9 | Viewed by 4656
Abstract
Ingestion of alcohol is associated with numerous changes in human energy metabolism, especially that of plasma lipids and lipoproteins. Regular moderate alcohol consumption is associated with reduced atherosclerotic cardiovascular disease (ASCVD), an effect that has been attributed to the concurrent elevations of plasma [...] Read more.
Ingestion of alcohol is associated with numerous changes in human energy metabolism, especially that of plasma lipids and lipoproteins. Regular moderate alcohol consumption is associated with reduced atherosclerotic cardiovascular disease (ASCVD), an effect that has been attributed to the concurrent elevations of plasma high-density lipoprotein-cholesterol (HDL-C) concentrations. More recent evidence has accrued against the hypothesis that raising plasma HDL concentrations prevents ASCVD so that other metabolic processes associated with alcohol consumption have been considered. This review explored the roles of other metabolites induced by alcohol consumption—triglyceride-rich lipoproteins, non-esterified free fatty acids, and acetate, the terminal alcohol metabolite in athero-protection: Current evidence suggests that acetate has a key role in athero-protection but additional studies are needed. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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20 pages, 291 KiB  
Review
High-Density Lipoprotein Cholesterol in Age-Related Ocular Diseases
by Bjorn Kaijun Betzler, Tyler Hyungtaek Rim, Charumathi Sabanayagam, Chui Ming Gemmy Cheung and Ching-Yu Cheng
Biomolecules 2020, 10(4), 645; https://doi.org/10.3390/biom10040645 - 22 Apr 2020
Cited by 18 | Viewed by 4370
Abstract
There is limited understanding of the specific role of high-density lipoprotein cholesterol (HDL-C) in the development of various age-related ocular diseases, despite it being a common measurable biomarker in lipid profiles. This literature review summarizes current knowledge of the role of HDL-C, if [...] Read more.
There is limited understanding of the specific role of high-density lipoprotein cholesterol (HDL-C) in the development of various age-related ocular diseases, despite it being a common measurable biomarker in lipid profiles. This literature review summarizes current knowledge of the role of HDL-C, if any, in pathogenesis and progression of four age-related ocular diseases, namely age-related macular degeneration (AMD), age-related cataract, glaucoma, and diabetic retinopathy (DR), and will primarily discuss epidemiological and genetic evidence. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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18 pages, 1234 KiB  
Review
High-Density Lipoproteins Are Bug Scavengers
by Olivier Meilhac, Sébastien Tanaka and David Couret
Biomolecules 2020, 10(4), 598; https://doi.org/10.3390/biom10040598 - 12 Apr 2020
Cited by 56 | Viewed by 7379
Abstract
Lipoproteins were initially defined according to their composition (lipids and proteins) and classified according to their density (from very low- to high-density lipoproteins—HDLs). Whereas their capacity to transport hydrophobic lipids in a hydrophilic environment (plasma) is not questionable, their primitive function of cholesterol [...] Read more.
Lipoproteins were initially defined according to their composition (lipids and proteins) and classified according to their density (from very low- to high-density lipoproteins—HDLs). Whereas their capacity to transport hydrophobic lipids in a hydrophilic environment (plasma) is not questionable, their primitive function of cholesterol transporter could be challenged. All lipoproteins are reported to bind and potentially neutralize bacterial lipopolysaccharides (LPS); this is particularly true for HDL particles. In addition, HDL levels are drastically decreased under infectious conditions such as sepsis, suggesting a potential role in the clearance of bacterial material and, particularly, LPS. Moreover, "omics" technologies have unveiled significant changes in HDL composition in different inflammatory states, ranging from acute inflammation occurring during septic shock to low-grade inflammation associated with moderate endotoxemia such as periodontal disease or obesity. In this review, we will discuss HDL modifications associated with exposure to pathogens including bacteria, viruses and parasites, with a special focus on sepsis and the potential of HDL therapy in this context. Low-grade inflammation associated with atherosclerosis, periodontitis or metabolic syndrome may also highlight the protective role of HDLs in theses pathologies by other mechanisms than the reverse transport of cholesterol. Full article
(This article belongs to the Special Issue High-Density Lipoprotein (HDL): The Role of Reverse Cholesterol Transport in Human Health and Disease)
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