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High-Density Lipoprotein (HDL) Metabolism and Functionality

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A special issue of Molecules (ISSN 1420-3049). This special issue belongs to the section "Macromolecular Chemistry".

Deadline for manuscript submissions: closed (31 January 2024) | Viewed by 9443

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Prof. Dr. Kyung-Hyun Cho

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Guest Editor

1. Korea Research Institute of Lipoproteins, Medical Innovation Complex, Daegu 41061, Republic of Korea
2. LipoLab, Yeungnam University, Gyeongsan 38541, Republic of Korea
Interests: high-density lipoprotein (HDL); apoA-I; atherosclerosis; Alzheimer’s disease and dementia; hypertension
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Dear Colleagues,

High-density lipoproteins (HDL) are a strong antioxidant, anti-inflammatory, and anti-senescence agent in blood. HDL cholesterol is inversely correlated with incidence of hypertension, atherosclerosis, and dementia. The metabolism of HDL is dynamic and reversible; HDL can be changed upon various health statuses, such as exercise, dietary patterns, exposure of infections, and environmental pollutions. HDL can be used for therapeutic tools and as a vehicle for drug delivery. HDL is a potent anti-thrombotic and anti-infectious (virus, bacteria, and protozoa) macromolecule in body fluids to maintain human health.

This Special Issue on “High-Density Lipoprotein (HDL) Metabolism and Functionality” welcomes original research and reviews on: (1) functional and structural correlations of HDL and apolipoproteins in various health statuses; (2) quantity and quality change of HDL in environmental stresses and infection; (3) improvement of HDL quality and prevention of cardiovascular diseases, Alzheimer’s disease, dementia, etc.; (4) clinical application of HDL to treat aging-related disease and acute-infection disease; and (5) practical tools and life-style modification for enhancement of HDL functionality

Prof. Dr. Kyung-Hyun Cho
Guest Editor

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Keywords

High-density lipoproteins (HDL)
HDL functionality
Apolipoproteins
Cardiovascular disease (CVD)
Alzheimer’s disease
Vascular dementia
Anti-infection
Heathy aging and longevity

Published Papers (4 papers)

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Research

24 pages, 12830 KiB

Open AccessArticle

Comparison of Policosanols via Incorporation into Reconstituted High-Density Lipoproteins: Cuban Policosanol (Raydel^®) Exerts the Highest Antioxidant, Anti-Glycation, and Anti-Inflammatory Activity

by Kyung-Hyun Cho, Ji-Eun Kim, Hyo-Seon Nam, Dae-Jin Kang and Seung-Hee Baek

Molecules 2023, 28(18), 6715; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules28186715 - 20 Sep 2023

Cited by 3 | Viewed by 1363

Abstract

Reconstituted high-density lipoproteins (rHDL) containing each policosanol from Cuba (Raydel^®), China (Shaanxi Pioneer), and the United States (Lesstanol^®) were synthesized to compare the physiological properties of policosanol depending on sources and origin countries. After synthesis with apolipoproteinA-I (apoA-I) into rHDL, all policosanols bound well with phospholipid and apoA-I to form discoidal rHDL. An rHDL containing Cuban policosanol (rHDL-1) showed the largest rHDL particle size of around 83 ± 3 nm, while rHDL containing Chinese policosanol (rHDL-2) or American policosanol (rHDL-3) showed smaller particles around 63 ± 3 nm and 60 ± 2 nm in diameter, respectively. The rHDL-1 showed the strongest anti-glycation activity to protect the apoA-I degradation of HDL from fructose-mediated glycation: approximately 2.7-times higher ability to suppress glycation and 1.4-times higher protection ability of apoA-I than that of rHDL-2 and rHDL-3. The rHDL-1 showed the highest antioxidant ability to inhibit cupric ion-mediated LDL oxidation in electromobility and the quantification of oxidized species. A microinjection of each rHDL into a zebrafish embryo in the presence of carboxymethyllysine (CML) showed that rHDL-1 displayed the strongest anti-oxidant activity with the highest embryo survivability, whereas rHDL-2 and rHDL-3 showed much weaker protection ability, similar to rHDL alone (rHDL-0). An intraperitoneal injection of CML (250 μg) into adult zebrafish caused acute death and hyperinflammation with an elevation of infiltration of neutrophils and IL-6 production in the liver. On the other hand, a co-injection of rHDL-1 resulted in the highest survivability and the strongest anti-inflammatory ability to suppress IL-6 production with an improvement of the blood lipid profile, such as elevation of HDL-C and lowering of the total cholesterol, LDL-cholesterol, and triglyceride. In conclusion, Cuban policosanol exhibited the most desirable properties for the in vitro synthesis of rHDL with the stabilization of apoA-I, the largest particle size, anti-glycation against fructation, and antioxidant activities to prevent LDL oxidation. Cuban policosanol in rHDL also exhibited the strongest in vivo antioxidant and anti-inflammatory activities with the highest survivability in zebrafish embryos and adults via the prevention of hyperinflammation in the presence of CML. Full article

(This article belongs to the Special Issue High-Density Lipoprotein (HDL) Metabolism and Functionality)

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19 pages, 2648 KiB

Open AccessArticle

Structural and Functional Changes of Reconstituted High-Density Lipoprotein (HDL) by Incorporation of α-synuclein: A Potent Antioxidant and Anti-Glycation Activity of α-synuclein and apoA-I in HDL at High Molar Ratio of α-synuclein

by Kyung-Hyun Cho

Molecules 2021, 26(24), 7485; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26247485 - 10 Dec 2021

Cited by 5 | Viewed by 2886

Abstract

α-synuclein (α-syn) is a major culprit of Parkinson’s disease (PD), although lipoprotein metabolism is very important in the pathogenesis of PD. α-syn was expressed and purified using the pET30a expression vector from an E. coli expression system to elucidate the physiological effects of α-syn on lipoprotein metabolism. The human α-syn protein (140 amino acids) with His-tag (8 amino acids) was expressed and purified to at least 95% purity. Isoelectric focusing gel electrophoresis showed that the isoelectric point (pI) of α-syn and apoA-I were pI = 4.5 and pI = 6.4, respectively. The lipid-free α-syn showed almost no phospholipid-binding ability, while apoA-I showed rapid binding ability with a half-time (T_1/2) = 8 ± 0.7 min. The α-syn and apoA-I could be incorporated into the reconstituted HDL (rHDL, molar ratio 95:5:1:1, palmitoyl-2-oleoyl-sn-glycero-3-phosphocholine (POPC):cholesterol:apoA-I:α-syn with the production of larger particles (92 Å) than apoA-I-rHDL (86 and 78 Å) and α-syn-rHDL (65 Å). An rHDL containing both apoA-I and α-syn showed lower α-helicity around 45% with a red shift of the Trp wavelength maximum fluorescence (WMF) from 339 nm, while apoA-I-HDL showed 76% α-helicity and 337 nm of WMF. The denaturation by urea addition showed that the incorporation of α-syn in rHDL caused a larger increase in the WMF than apoA-I-rHDL, suggesting that the destabilization of the secondary structure of apoA-I by the addition of α-syn. On the other hand, the addition of α-syn induced two-times higher resistance to rHDL glycation at apoA-I:α-syn molar ratios of 1:1 and 1:2. Interestingly, low α-syn in rHDL concentrations, molar ratio of 1:0.5 (apoA-I:α-syn), did not prevent glycation with more multimerization of apoA-I. In the lipid-free and lipid-bound state, α-syn showed more potent antioxidant activity than apoA-I against cupric ion-mediated LDL oxidation. On the other hand, microinjection of α-syn (final 2 μM) resulted in 10% less survival of zebrafish embryos than apoA-I. A subcutaneous injection of α-syn (final 34 μM) resulted in less tail fin regeneration than apoA-I. Interestingly, incorporation of α-syn at a low molar ratio (apoA-I:α-syn, 1:0.5) in rHDL resulted destabilization of the secondary structure and impairment of apoA-I functionality via more oxidation and glycation. However, at a higher molar ratio of α-syn in rHDL (apoA-I:α-syn = 1:1 or 1:2) exhibited potent antioxidant and anti-glycation activity without aggregation. In conclusion, there might be a critical concentration of α-syn and apoA-I in HDL-like complex to prevent the aggregation of apoA-I via structural and functional enhancement. Full article

(This article belongs to the Special Issue High-Density Lipoprotein (HDL) Metabolism and Functionality)

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11 pages, 818 KiB

Open AccessArticle

Assessing HDL Metabolism in Subjects with Elevated Levels of HDL Cholesterol and Coronary Artery Disease

by William Hancock-Cerutti, John S. Millar, Silvia Valentini, Jason Liu, Jeffrey T. Billheimer, Daniel J. Rader and Marina Cuchel

Molecules 2021, 26(22), 6862; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26226862 - 14 Nov 2021

Cited by 3 | Viewed by 2048

Abstract

High-density lipoprotein cholesterol (HDL-C) is thought to be atheroprotective yet some patients with elevated HDL-C levels develop cardiovascular disease, possibly due to the presence of dysfunctional HDL. We aimed to assess the metabolic fate of circulating HDL particles in patients with high HDL-C with and without coronary artery disease (CAD) using in vivo dual labeling of its cholesterol and protein moieties. We measured HDL apolipoprotein (apo) A-I, apoA-II, free cholesterol (FC), and cholesteryl ester (CE) kinetics using stable isotope-labeled tracers (D₃-leucine and ¹³C₂-acetate) as well as ex vivo cholesterol efflux to HDL in subjects with (n = 6) and without (n = 6) CAD that had HDL-C levels >90th percentile. Healthy controls with HDL-C within the normal range (n = 6) who underwent the same procedures were used as the reference. Subjects with high HDL-C with and without CAD had similar plasma lipid levels and similar apoA-I, apoA-II, HDL FC, and CE pool sizes with no significant differences in fractional clearance rates (FCRs) or production rates (PRs) of these components between groups. Subjects with high HDL-C with and without CAD also had similar basal and cAMP-stimulated ex vivo cholesterol efflux to HDL. When all subjects were considered (n = 18), unstimulated non-ABCA1-mediated efflux (but not ABCA1-specific efflux) was correlated positively with apoA-I production (r = 0.552, p = 0.017) and HDL FC and CE pool sizes, and negatively with the fractional clearance rate of FC (r = −0.759, p = 4.1 × 10⁻⁴) and CE (r = −0.652, p = 4.57 × 10⁻³). Our data are consistent with the concept that ex vivo non-ABCA1 efflux capacity may correlate with slower in vivo turnover of HDL cholesterol moieties. The use of a dual labeling protocol provided for the first time the opportunity to assess the association of ex vivo cholesterol efflux capacity with in vivo HDL cholesterol metabolic parameters. Full article

(This article belongs to the Special Issue High-Density Lipoprotein (HDL) Metabolism and Functionality)

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12 pages, 1533 KiB

Open AccessArticle

Lack of Neuroprotective Effects of High-Density Lipoprotein Therapy in Stroke under Acute Hyperglycemic Conditions

by David Couret, Cynthia Planesse, Jessica Patche, Nicolas Diotel, Brice Nativel, Steeve Bourane and Olivier Meilhac

Molecules 2021, 26(21), 6365; https://0-doi-org.brum.beds.ac.uk/10.3390/molecules26216365 - 21 Oct 2021

Cited by 4 | Viewed by 1707

Abstract

Introduction: The pleiotropic protective effects of high-density lipoproteins (HDLs) on cerebral ischemia have never been tested under acute hyperglycemic conditions. The aim of this study is to evaluate the potential neuroprotective effect of HDL intracarotid injection in a mouse model of middle cerebral artery occlusion (MCAO) under hyperglycemic conditions. Methods: Forty-two mice were randomized to receive either an intracarotid injection of HDLs or saline. Acute hyperglycemia was induced by an intraperitoneal injection of glucose (2.2 g/kg) 20 min before MCAO. Infarct size (2,3,5-triphenyltetrazolium chloride (TTC)-staining), blood–brain barrier leakage (IgG infiltration), and hemorrhagic changes (hemoglobin assay by ELISA and hemorrhagic transformation score) were analyzed 24 h post-stroke. Brain tissue inflammation (IL-6 by ELISA, neutrophil infiltration and myeloperoxidase by immunohisto-fluorescence) and apoptosis (caspase 3 activation) were also assessed. Results: Intraperitoneal D-glucose injection allowed HDL- and saline-treated groups to reach a blood glucose level of 300 mg/dl in the acute phase of cerebral ischemia. HDL injection did not significantly reduce mortality (19% versus 29% in the saline-injected group) or cerebral infarct size (p = 0.25). Hemorrhagic transformations and inflammation parameters were not different between the two groups. In addition, HDL did not inhibit apoptosis under acute hyperglycemic conditions. Conclusion: We observed a nonsignificant decrease in cerebral infarct size in the HDL group. The deleterious consequences of reperfusion such as hemorrhagic transformation or inflammation were not improved by HDL infusion. In acute hyperglycemia, HDLs are not potent enough to counteract the adverse effects of hyperglycemia. The addition of antioxidants to therapeutic HDLs could improve their neuroprotective capacity. Full article

(This article belongs to the Special Issue High-Density Lipoprotein (HDL) Metabolism and Functionality)

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