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Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact

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A special issue of International Journal of Molecular Sciences (ISSN 1422-0067). This special issue belongs to the section "Biochemistry".

Deadline for manuscript submissions: closed (30 November 2022) | Viewed by 23080

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Special Issue Editor

Prof. Dr. Kyung-Hyun Cho

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Guest Editor

LipoLab, Department of Medical Biotechnology, Yeungnam University, Gyeongsan 712-749, Republic of Korea
Interests: high-density lipoprotein (HDL); apoA-I; atherosclerosis; Alzheimer’s disease and dementia; hypertension
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Accumulated studies demonstrated that many aspects of high-density lipoprotein (HDL) in human growth, human disease, and aging process under different environmental changes. HDL can be changed upon various health statuses, such as exercise, dietary patterns, exposure of infections, and environmental pollutions. HDL can be a good biomarker to diagnose many diseases and its progression via the monitoring of changes in its antioxidant and anti-inflammation abilities. Dysfunctional HDL has poor HDL quality, such as less apoA-I content, lower antioxidant ability, and smaller size.

Quantity and quality of HDL can influence properties of LDL, which is considered as major culprit of cardiovascular disease (CVD). More oxidized and glycated LDL is prone to accelerate more incidence of cerebrovascular disease as well as CVD. Therefore, enhancement of HDL quantity and quality could be a good tool to suppress many diseases of heart and brain. Regarding COVID-19, HDL functionality, particularly paraoxonase (PON-1) activity, might be important for suppressing a SARS-CoV-2 infection. Native HDL with antioxidant and anti-atherosclerotic activity displayed potent antiviral activity to suppress the replication of SARS-CoV-2, while glycated HDL lost its antiviral activity.

In this special issue, I would elect to focus on functional and structural correlations of HDL and LDL in various health statuses, and the roles of HDL-associated apolipoproteins and enzymes as therapeutic tools.

Prof. Dr. Kyung-Hyun Cho
Guest Editor

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Keywords

high-density lipoproteins (HDL)
low-density lipoproteins (LDL)
HDL functionality
LDL oxidation
apolipoproteins
cardiovascular disease (CVD)
Alzheimer’s disease
vascular dementia
anti-infection

Published Papers (8 papers)

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Research

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18 pages, 3454 KiB

Open AccessArticle

Enhancement of High-Density Lipoprotein (HDL) Quantity and Quality by Regular and Habitual Exercise in Middle-Aged Women with Improvements in Lipid and Apolipoprotein Profiles: Larger Particle Size and Higher Antioxidant Ability of HDL

by Kyung-Hyun Cho, Hyo-Seon Nam, Dae-Jin Kang, Seonggeun Zee and Min-Hee Park

Int. J. Mol. Sci. 2023, 24(2), 1151; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24021151 - 06 Jan 2023

Cited by 8 | Viewed by 1883

Abstract

Regular exercise, especially aerobic exercise, is beneficial for increasing serum high-density lipoprotein-cholesterol (HDL-C) levels in the general population. In addition to the HDL-C quantity, exercise enhances HDL functionality, antioxidants, and cholesterol efflux. On the other hand, the optimal intensity and frequency of exercise to increase HDL quantity and enhance HDL quality in middle-aged women need to be determined. The current study was designed to compare the changes in HDL quantity and quality among middle-aged women depending on exercise intensity, frequency, and duration; participants were divided into a sedentary group (group 1), a middle-intensity group (group 2), and a high-intensity group (group 3). There were no differences in anthropometric parameters among the groups, including blood pressure, muscle mass, and handgrip strength. Although there was no difference in serum total cholesterol (TC) among the groups, the serum HDL-C and apolipoprotein (apo)A-I levels remarkably increased to 17% and 12%, respectively, in group 3. Serum low-density lipoprotein-cholesterol (LDL-C), glucose, triglyceride, and the apo-B/apoA-I ratio were remarkably decreased in the exercise groups depending on the exercise intensity; group 3 showed 13%, 10%, and 45% lower LDL-C, glucose, and triglyceride (TG), respectively, than group 1. The hepatic and muscle damage parameter, aspartate aminotransferase (AST), was significantly decreased in the exercise groups, but high-sensitivity C-reactive protein (CRP), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GTP) were similar in the three groups. In LDL, the particle size was increased 1.5-fold (p < 0.001), and the oxidation extent was decreased by 40% with a 23% lower TG content in group 3 than in group 1. In the exercise groups (groups 2 and 3), LDL showed the slowest electromobility with a distinct band intensity compared to the sedentary group (group 1). In HDL₂, the particle size was 2.1-fold increased (p < 0.001) in the exercise group (group 3) with a 1.5-fold increase in TC content compared to that in group 1, as well as significantly enhanced antioxidant abilities, paraoxonase (PON) activity, and ferric ion reduction ability (FRA). In HDL₃, the particle size was increased 1.2-fold with a 45% reduction in TG in group 3 compared to group 1. With increasing exercise intensity, apoA-I expression was increased in HDL₂ and HDL₃, and PON activity and FRA were enhanced (p < 0.001). In conclusion, regular exercise in middle-aged women is associated with the elevation of serum HDL-C and apoA-I with the enhancement of HDL quality and functionality and an increase in the TC content, particle size, and antioxidant abilities. With the reduction in TG and oxidized products in LDL and HDL, lipoproteins could have more anti-atherogenic properties through regular exercise in an intensity-dependent manner. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact)

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16 pages, 1669 KiB

Open AccessArticle

Osteoblast Demineralization Induced by Oxidized High-Density Lipoprotein via the Inflammatory Pathway Is Suppressed by Adiponectin

by Noor Hanisa Harun, Gabriele Ruth Anisah Froemming, Aletza Mohd Ismail, Hapizah Nawawi, Siti Shuhada Mokhtar and Suhaila Abd Muid

Int. J. Mol. Sci. 2022, 23(23), 14616; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232314616 - 23 Nov 2022

Cited by 2 | Viewed by 1098

Abstract

Low mineralization activity by human osteoblast cells (HOBs) indicates abnormal bone remodeling that potentially leads to osteoporosis. Oxidation, the most prominent form of high-density lipoprotein (HDL) modification, is suggested to affect bone mineralization through the inflammatory pathway. Adiponectin, which possesses anti-inflammatory activity, is postulated to have the ability to suppress the detrimental effects of oxidized HDL (oxHDL). This study aimed to investigate the effects of HDL before and after oxidation on markers of mineralization and inflammation. The protective effects of adiponectin on demineralization and inflammation induced by oxHDL were also investigated. OxHDL at 100 µg/mL protein had the highest inhibitory effect on mineralization, followed by lower calcium incorporation. OxHDL also had significantly lower expression of a mineralization marker (COL1A2) and higher expression of inflammatory markers (IL-6, TNF-α, and RELA proto-oncogene, NF-κβ (p65)) compared to the unstimulated control group. These findings suggest that oxHDL reduces the mineralization activity of HOBs by increasing the expression of inflammatory markers. Interestingly, co-incubation of adiponectin and oxHDL in HOBs resulted in higher expression of mineralization markers (ALPL, COL1A2, BGLAP, and RUNX2) and significantly reduced all targeted inflammatory markers compared to the oxHDL groups. On the contrary, HDL increased the expression of mineralization markers (COL1A2 and STAT-3) and exhibited lower expression of inflammatory cytokines (IL-6 and TNF-α), proving the protective effect of HDL beyond the reverse cholesterol transport activity. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact)

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14 pages, 351 KiB

Open AccessArticle

Blood Analytes as Biomarkers of Mechanisms Involved in Alzheimer’s Disease Progression

by Andrea Baldini, Alberto Greco, Mirko Lomi, Roberta Giannelli, Paola Canale, Andrea Diana, Cristina Dolciotti, Renata Del Carratore and Paolo Bongioanni

Int. J. Mol. Sci. 2022, 23(21), 13289; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms232113289 - 31 Oct 2022

Cited by 3 | Viewed by 1868

Abstract

Alzheimer’s disease (AD) is the leading cause of dementia, but the pathogenetic factors are not yet well known, and the relationships between brain and systemic biochemical derangements and disease onset and progression are unclear. We aim to focus on blood biomarkers for an accurate prognosis of the disease. We used a dataset characterized by longitudinal findings collected over the past 10 years from 90 AD patients. The dataset included 277 observations (both clinical and biochemical ones, encompassing blood analytes encompassing routine profiles for different organs, together with immunoinflammatory and oxidative markers). Subjects were grouped into four severity classes according to the Clinical Dementia Rating (CDR) Scale: mild (CDR = 0.5 and CDR = 1), moderate (CDR = 2), severe (CDR = 3) and very severe (CDR = 4 and CDR = 5). Statistical models were used for the identification of potential blood markers of AD progression. Moreover, we employed the Pathfinder tool of the Reactome database to investigate the biological pathways in which the analytes of interest could be involved. Statistical results reveal an inverse significant relation between four analytes (high-density cholesterol, total cholesterol, iron and ferritin) with AD severity. In addition, the Reactome database suggests that such analytes could be involved in pathways that are altered in AD progression. Indeed, the identified blood markers include molecules that reflect the heterogeneous pathogenetic mechanisms of AD. The combination of such blood analytes might be an early indicator of AD progression and constitute useful therapeutic targets. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact)

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19 pages, 4902 KiB

Open AccessArticle

Anti-Inflammatory Activity of CIGB-258 against Acute Toxicity of Carboxymethyllysine in Paralyzed Zebrafish via Enhancement of High-Density Lipoproteins Stability and Functionality

by Kyung-Hyun Cho, Ji-Eun Kim, Hyo-Seon Nam, Dae-Jin Kang and Hye-Jee Na

Int. J. Mol. Sci. 2022, 23(17), 10130; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms231710130 - 04 Sep 2022

Cited by 11 | Viewed by 1901

Abstract

Background: Hyperinflammation is frequently associated with the chronic pain of autoimmune disease and the acute death of coronavirus disease (COVID-19) via a severe cytokine cascade. CIGB-258 (Jusvinza^®), an altered peptide ligand with 3 kDa from heat shock protein 60 (HSP60), inhibits the systemic inflammation and cytokine storm, but the precise mechanism is still unknown. Objective: The protective effect of CIGB-258 against inflammatory stress of N-ε-carboxymethyllysine (CML) was tested to provide mechanistic insight. Methods: CIGB-258 was treated to high-density lipoproteins (HDL) and injected into zebrafish and its embryo to test a putative anti-inflammatory activity under presence of CML. Results: Treatment of CML (final 200 μM) caused remarkable glycation of HDL with severe aggregation of HDL particles to produce dysfunctional HDL, which is associated with a decrease in apolipoprotein A-I stability and lowered paraoxonase activity. Degradation of HDL₃ by ferrous ions was attenuated by a co-treatment with CIGB-258 with a red-shift of the Trp fluorescence in HDL. A microinjection of CML (500 ng) into zebrafish embryos resulted in the highest embryo death rate, only 18% of survivability with developmental defects. However, co-injection of CIGB-258 (final 1 ng) caused the remarkable elevation of survivability around 58%, as well as normal developmental speed. An intraperitoneal injection of CML (final 250 μg) into adult zebrafish resulted acute paralysis, sudden death, and laying down on the bottom of the cage with no swimming ability via neurotoxicity and inflammation. However, a co-injection of CIGB-258 (1 μg) resulted in faster recovery of the swimming ability and higher survivability than CML alone injection. The CML alone group showed 49% survivability, while the CIGB-258 group showed 97% survivability (p < 0.001) with a remarkable decrease in hepatic inflammation up to 50%. A comparison of efficacy with CIGB-258, Infliximab (Remsima^®), and Tocilizumab (Actemra^®) showed that the CIGB-258 group exhibited faster recovery and swimming ability with higher survivability than those of the Infliximab group. The CIGB-258 group and Tocilizumab group showed the highest survivability, the lowest plasma total cholesterol and triglyceride level, and the infiltration of inflammatory cells, such as neutrophils in hepatic tissue. Conclusion: CIGB-258 ameliorated the acute neurotoxicity, paralysis, hyperinflammation, and death induced by CML, resulting in higher survivability in zebrafish and its embryos by enhancing the HDL structure and functionality. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact)

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16 pages, 2695 KiB

Open AccessArticle

Long-Term Alcohol Consumption Caused a Significant Decrease in Serum High-Density Lipoprotein (HDL)-Cholesterol and Apolipoprotein A-I with the Atherogenic Changes of HDL in Middle-Aged Korean Women

by Kyung-Hyun Cho, Hyo-Seon Nam, Dae-Jin Kang, Min-Hee Park and Ju-Hyun Kim

Int. J. Mol. Sci. 2022, 23(15), 8623; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23158623 - 03 Aug 2022

Cited by 14 | Viewed by 3431

Abstract

Light-to-moderate alcohol drinking is associated with a low incidence of cardiovascular disease (CVD) via an elevation of high-density lipoproteins-cholesterol (HDL-C), particularly with the short-term supplementation of alcohol. However, there is no information on the change in the HDL qualities and functionalities between non-drinkers and mild drinkers in the long-term consumption of alcohol. This study analyzed the lipid and lipoprotein profiles of middle-aged Korean female non-drinkers, mild-drinkers, and binge-drinkers, who consumed alcohol for at least 10 years. Unexpectedly, the serum levels of HDL-C and apolipoprotein A-I (apoA-I) were decreased significantly depending on the alcohol amount; the binge-drinker group showed 18% and 13% lower HDL-C (p = 0.011) and apoA-I levels (p = 0.024), respectively, than the non-drinker group. Triglyceride (TG) and oxidized species, malondialdehyde (MDA), and low-density lipoproteins (LDL) levels were significantly elevated in the drinker groups. Interestingly, the binge-drinker group showed 1.4-fold higher (p = 0.020) cholesterol contents in HDL₂ and 1.7-fold higher (p < 0.001) TG contents in HDL₃ than those of the non-drinker group. The mild-drinker group also showed higher TG contents in HDL₃ (p = 0.032) than the non-drinker group, while cholesterol contents were similar in the HDL₃ of all groups. Transmission electron microscopy (TEM) showed that the non-drinker group showed a more distinct and clear particle shape of the LDL and HDL image with a larger particle size than the drinker group. Electrophoresis of LDL showed that the drinker group had faster electromobility with a higher smear band intensity and aggregation in the loading position than the non-drinker group. The HDL level of binge drinkers showed the lowest paraoxonase activity, the highest glycated extent, and the most smear band intensity of HDL and apoA-I, indicating that HDL quality and functionality were impaired by alcohol consumption. In conclusion, long-term alcohol consumption in middle-aged women, even in small amounts, caused a significant decrease in the serum HDL-C and apoA-I with atherogenic changes in LDL and HDL, such as an increase in TG and MDA content with a loss of paraoxonase activity. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact)

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18 pages, 3094 KiB

Open AccessArticle

Genetic Evidence for a Causal Relationship between Hyperlipidemia and Type 2 Diabetes in Mice

by Lisa J. Shi, Xiwei Tang, Jiang He and Weibin Shi

Int. J. Mol. Sci. 2022, 23(11), 6184; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23116184 - 31 May 2022

Cited by 2 | Viewed by 1665

Abstract

Dyslipidemia is considered a risk factor for type 2 diabetes (T2D), yet studies with statins and candidate genes suggest that circulating lipids may protect against T2D development. Apoe-null (Apoe^-/-) mouse strains develop spontaneous dyslipidemia and exhibit a wide variation in susceptibility to diet-induced T2D. We thus used Apoe^-/- mice to elucidate phenotypic and genetic relationships of circulating lipids with T2D. A male F2 cohort was generated from an intercross between LP/J and BALB/cJ Apoe^-/- mice and fed 12 weeks of a Western diet. Fasting, non-fasting plasma glucose, and lipid levels were measured and genotyping was performed using miniMUGA arrays. We uncovered a major QTL near 60 Mb on chromosome 15, Nhdlq18, which affected non-HDL cholesterol and triglyceride levels under both fasting and non-fasting states. This QTL was coincident with Bglu20, a QTL that modulates fasting and non-fasting glucose levels. The plasma levels of non-HDL cholesterol and triglycerides were closely correlated with the plasma glucose levels in F2 mice. Bglu20 disappeared after adjustment for non-HDL cholesterol or triglycerides. These results demonstrate a causative role for dyslipidemia in T2D development in mice. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact)

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13 pages, 873 KiB

Open AccessArticle

Atherogenic Plasma Index or Non-High-Density Lipoproteins as Markers Best Reflecting Age-Related High Concentrations of Small Dense Low-Density Lipoproteins

by Sylwia Płaczkowska, Katarzyna Sołkiewicz, Iwona Bednarz-Misa and Ewa Maria Kratz

Int. J. Mol. Sci. 2022, 23(9), 5089; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms23095089 - 03 May 2022

Cited by 9 | Viewed by 1711

Abstract

The study aimed to assess the strength of the relationships between small dense low-density lipoproteins (sdLDL) and other parameters describing metabolic disorders and determine which of the lipid profile parameters can be used as markers of increased sdLDL concentration. The proposed model of sdLDL (examined by heparin–magnesium precipitation method) as a function of lipid parameters and atherogenic plasma indexes non-high-dense lipoproteins (non-HDL) and total cholesterol to high-dense lipoprotein ratio (TC/HDL), Atherogenic plasma index (API) is based on data from 485 participants divided into two age groups, <35≥ years. In multiple linear regression, sdLDL concentration was associated with the concentration of non-HDL-C (p = 0.043) and API value (p < 0.001) in participants <35 years, and with non-HDL-C (p < 0.001) and triglycerides (p = 0.020) concentration ≥35 years. The presence of abnormal values of API in participants <35 years and non-HDL-C in participants ≥35 years is a significant factor increasing the chances of the highest sdLDL (≥1.03 mmol/L) corresponding to Q4 in people without metabolic disorders. Different lipid parameters and atherogenicity indexes are associated with a high concentration of sdLDL depending on the age group. Abnormal API <35 years and non-HDL ≥35 years are associated with the highest sdLDL values and may be an indication for further specialist diagnosis of cardiovascular disease risk factors. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact)

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Review

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23 pages, 769 KiB

Open AccessReview

The Impact of Aerobic Exercise on HDL Quantity and Quality: A Narrative Review

by Beata Franczyk, Anna Gluba-Brzózka, Aleksandra Ciałkowska-Rysz, Janusz Ławiński and Jacek Rysz

Int. J. Mol. Sci. 2023, 24(5), 4653; https://0-doi-org.brum.beds.ac.uk/10.3390/ijms24054653 - 28 Feb 2023

Cited by 18 | Viewed by 7569

Abstract

High-density lipoproteins comprise roughly 25–30% of the circulating proteins involved in the transport of lipids in circulation. These particles differ in size and lipid composition. Recent evidence suggests that the quality of HDL particles (which depends on shape, size and the composition of proteins and lipids determining HDL functionality) may be more important than their quantity. The functionality of HDL is mirrored by its cholesterol efflux activity, as well as its antioxidant (including the protection of LDL against oxidation), anti-inflammatory and antithrombotic properties. The results of many studies and meta-analyses imply the beneficial impact of aerobic exercise on HDL-C levels. Physical activity was found to be usually associated with an increase in HDL cholesterol and a decrease in LDL cholesterol and triglycerides. Exercise, apart from inducing quantitative alterations in serum lipids, exerts a beneficial impact on HDL particle maturation, composition and functionality. The Physical Activity Guidelines Advisory Committee Report underlined the importance of establishing a program recommending exercises that enable attainment of maximal advantage at the lowest level of risk. The aim of this manuscript is to review the impact of different types of aerobic exercise (various intensities and durations) on the level and quality of HDL. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact)

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