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Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact 2.0

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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 January 2024) | Viewed by 10541

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Prof. Dr. Kyung-Hyun Cho

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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
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Dear Colleagues,

Accumulated studies have demonstrated many aspects of high-density lipoprotein (HDL) in human growth, human disease, and the 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 a lower apoA-I content, lower antioxidant ability, and smaller size.

The quantity and quality of HDL can influence properties of LDL, which is considered to be a major cause of cardiovascular disease (CVD). More oxidized and glycated LDL is prone to accelerate the incidence of cerebrovascular disease as well as CVD. Therefore, the 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 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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Published Papers (5 papers)

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Research

23 pages, 4135 KiB

Open AccessArticle

Alcohol Consumption, High-Density Lipoprotein Particles and Subspecies, and Risk of Cardiovascular Disease: Findings from the PREVEND Prospective Study

by Setor K. Kunutsor, Atanu Bhattacharjee, Margery A. Connelly, Stephan J. L. Bakker and Robin P. F. Dullaart

Int. J. Mol. Sci. 2024, 25(4), 2290; https://doi.org/10.3390/ijms25042290 - 14 Feb 2024

Cited by 1 | Viewed by 701

Abstract

The associations of HDL particle (HDL-P) and subspecies concentrations with alcohol consumption are unclear. We aimed to evaluate the interplay between alcohol consumption, HDL parameters and cardiovascular disease (CVD) risk. In the PREVEND study of 5151 participants (mean age, 53 years; 47.5% males), self-reported alcohol consumption and HDL-P and subspecies (small, medium, and large) by nuclear magnetic resonance spectroscopy were assessed. Hazard ratios (HRs) with 95% CIs for first CVD events were estimated. In multivariable linear regression analyses, increasing alcohol consumption increased HDL-C, HDL-P, large and medium HDL, HDL size, and HDL subspecies (H3P, H4P, H6 and H7) in a dose-dependent manner. During a median follow-up of 8.3 years, 323 first CVD events were recorded. Compared with abstainers, the multivariable adjusted HRs (95% CIs) of CVD for occasional to light, moderate, and heavy alcohol consumers were 0.72 (0.55–0.94), 0.74 (0.54–1.02), and 0.65 (0.38–1.09), respectively. These associations remained consistent on additional adjustment for each HDL parameter. For CVD, only HDL-C was associated with a statistically significant decreased risk of CVD in a fully adjusted analysis (HR 0.84, 95% CI 0.72–0.97 per 1 SD increment). For coronary heart disease, HDL-C, HDL-P, medium HDL, HDL size, and H4P showed inverse associations, whereas HDL-C and HDL size modestly increased stroke risk. Except for H6P, alcohol consumption did not modify the associations between HDL parameters and CVD risk. The addition of HDL-C, HDL size, or H4P to a CVD risk prediction model containing established risk factors improved risk discrimination. Increasing alcohol consumption is associated with increased HDL-C, HDL-P, large and medium HDL, HDL size, and some HDL subspecies. Associations of alcohol consumption with CVD are largely independent of HDL parameters. The associations of HDL parameters with incident CVD are generally not attenuated or modified by alcohol consumption. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact 2.0)

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13 pages, 1350 KiB

Open AccessArticle

Gender-Dependent Associations between Serum Betatrophin Levels and Lipoprotein Subfractions in Diabetic and Nondiabetic Obese Patients

by Hajnalka Lőrincz, Sára Csiha, Balázs Ratku, Sándor Somodi, Ferenc Sztanek, Ildikó Seres, György Paragh and Mariann Harangi

Int. J. Mol. Sci. 2023, 24(22), 16504; https://doi.org/10.3390/ijms242216504 - 19 Nov 2023

Viewed by 717

Abstract

Betatrophin, also known as angiopoietin-like protein 8 (ANGPTL8), mainly plays a role in lipid metabolism. To date, associations between betatrophin and lipoprotein subfractions are poorly investigated. For this study, 50 obese patients with type 2 diabetes (T2D) and 70 nondiabetic obese (NDO) subjects matched in gender, age, and body mass index (BMI) as well as 49 gender- and age-matched healthy, normal-weight controls were enrolled. Serum betatrophin levels were measured with ELISA, and lipoprotein subfractions were analyzed using Lipoprint gel electrophoresis. Betatrophin concentrations were found to be significantly higher in the T2D and NDO groups compared to the controls in all subjects and in females, but not in males. We found significant positive correlations between triglyceride, very low density lipoprotein (VLDL), large LDL (low density lipoprotein), small LDL, high density lipoprotein (HDL) -6-10 subfractions, and betatrophin, while negative correlations were detected between betatrophin and IDL, mean LDL size, and HDL-1-5. Proportion of small HDL was the best predictor of betatrophin in all subjects. Small LDL and large HDL subfractions were found to be the best predictors in females, while in males, VLDL was found to be the best predictor of betatrophin. Our results underline the significance of serum betatrophin measurement in the cardiovascular risk assessment of obese patients with and without T2D, but gender differences might be taken into consideration. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact 2.0)

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27 pages, 6087 KiB

Open AccessArticle

CIGB-258 Exerts Potent Anti-Inflammatory Activity against Carboxymethyllysine-Induced Acute Inflammation in Hyperlipidemic Zebrafish via the Protection of Apolipoprotein A-I

by Kyung-Hyun Cho, Hyo-Seon Nam, Ji-Eun Kim, Hye-Jee Na, Maria del Carmen Dominguez-Horta and Gillian Martinez-Donato

Int. J. Mol. Sci. 2023, 24(8), 7044; https://doi.org/10.3390/ijms24087044 - 11 Apr 2023

Cited by 8 | Viewed by 1904

Abstract

Inflammation and atherosclerosis are intimately associated via the production of dysfunctional high-density lipoproteins (HDL) and modification of apolipoprotein (apo) A-I. A putative interaction between CIGB-258 and apoA-I was investigated to provide mechanistic insight into the protection of HDL. The protective activity of CIGB-258 was tested in the CML-mediated glycation of apoA-I. The in vivo anti-inflammatory efficacy was compared in paralyzed hyperlipidemic zebrafish and its embryo in the presence of CML. Treatment of CML induced greater glycation extent of HDL/apoA-I and proteolytic degradation of apoA-I. In the presence of CML, however, co-treatment of CIGB-258 inhibited the glycation of apoA-I and protected the degradation of apoA-I, exerting enhanced ferric ion reduction ability. Microinjection of CML (500 ng) into zebrafish embryos resulted in acute death with the lowest survivability with severe developmental defects with interleukin (IL)-6 production. Conversely, a co-injection of CIGB-258 or Tocilizumab produced the highest survivability with a normal development speed and morphology. In hyperlipidemic zebrafish, intraperitoneal injection of CML (500 μg) caused the complete loss of swimming ability and severe acute death with only 13% survivability 3 h post-injection. A co-injection of the CIGB-258 resulted in a 2.2-fold faster recovery of swimming ability than CML alone, with higher survivability of approximately 57%. These results suggest that CIGB-258 protected hyperlipidemic zebrafish from the acute neurotoxicity of CML. Histological analysis showed that the CIGB-258 group had 37% lower infiltration of neutrophils in hepatic tissue and 70% lower fatty liver changes than those of the CML-alone group. The CIGB-258 group exhibited the smallest IL-6 expression in the liver and the lowest blood triglyceride level. CIGB-258 displayed potent anti-inflammatory activity in hyperlipidemic zebrafish by inhibiting apoA-I glycation, promoting rapid recovery from the paralysis of CML toxicity and suppression of IL-6, and lowering fatty liver changes. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact 2.0)

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24 pages, 7298 KiB

Open AccessArticle

Beneficial Effect of Cuban Policosanol on Blood Pressure and Serum Lipoproteins Accompanied with Lowered Glycated Hemoglobin and Enhanced High-Density Lipoprotein Functionalities in a Randomized, Placebo-Controlled, and Double-Blinded Trial with Healthy Japanese

by Kyung-Hyun Cho, Hyo-Seon Nam, Seung-Hee Baek, Dae-Jin Kang, Hyejee Na, Tomohiro Komatsu and Yoshinari Uehara

Int. J. Mol. Sci. 2023, 24(6), 5185; https://doi.org/10.3390/ijms24065185 - 08 Mar 2023

Cited by 10 | Viewed by 3852

Abstract

This study evaluated the efficacy and safety of 20 mg of Cuban policosanol in blood pressure (BP) and lipid/lipoprotein parameters of healthy Japanese subjects via a placebo-controlled, randomized, and double-blinded human trial. After 12 weeks of consumption, the policosanol group showed significantly lower BP, glycated hemoglobin (HbA_1c), and blood urea nitrogen (BUN) levels. The policosanol group also showed lower aspartate aminotransferase (AST), alanine aminotransferase (ALT), and γ-glutamyl transferase (γ-GTP) levels at week 12 than those at week 0: A decrease of up to 9% (p < 0.05), 17% (p < 0.05), and 15% (p < 0.05) was observed, respectively. The policosanol group showed significantly higher HDL-C level and HDL-C/TC (%), approximately 9.5% (p < 0.001) and 7.2% (p = 0.003), respectively, than the placebo group and a difference in the point of time and group interaction (p < 0.001). In lipoprotein analysis, the policosanol group showed a decrease in oxidation and glycation extent in VLDL and LDL with an improvement of particle shape and morphology after 12 weeks. HDL from the policosanol group showed in vitro stronger antioxidant and in vivo anti-inflammatory abilities. In conclusion, 12 weeks of Cuban policosanolconsumption in Japanese subjects showed significant improvement in blood pressure, lipid profiles, hepatic functions, and HbA_1c with enhancement of HDL functionalities. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact 2.0)

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20 pages, 3247 KiB

Open AccessArticle

Cuban Sugar Cane Wax Alcohol Exhibited Enhanced Antioxidant, Anti-Glycation and Anti-Inflammatory Activity in Reconstituted High-Density Lipoprotein (rHDL) with Improved Structural and Functional Correlations: Comparison of Various Policosanols

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

Int. J. Mol. Sci. 2023, 24(4), 3186; https://doi.org/10.3390/ijms24043186 - 06 Feb 2023

Cited by 8 | Viewed by 2190

Abstract

Policosanols from various sources, such as sugar cane, rice bran, and insects, have been marketed to prevent dyslipidemia, diabetes, and hypertension by increasing the blood high-density lipoproteins cholesterol (HDL-C) levels. On the other hand, there has been no study on how each policosanol influences the quality of HDL particles and their functionality. Reconstituted high-density lipoproteins (rHDLs) with apolipoprotein (apo) A-I and each policosanol were synthesized using the sodium cholate dialysis method to compare the policosanols in lipoprotein metabolism. Each rHDL was compared regarding the particle size and shape, antioxidant activity, and anti-inflammatory activity in vitro and in zebrafish embryos. This study compared four policosanols including one policosanol from Cuba (Raydel^® policosanol) and three policosanols from China (Xi’an Natural sugar cane, Xi’an Realin sugar cane, and Shaanxi rice bran). The synthesis of rHDLs with various policosanols (PCO) from Cuba or China using a molar ratio of 95:5:1:1 with palmitoyloleoyl phosphatidylcholine (POPC): free cholesterol (FC): apoA-I:PCO (wt:wt) showed that rHDL containing Cuban policosanol (rHDL-1) showed the largest particle size and the most distinct particle shape. The rHDL-1 showed a 23% larger particle diameter and increased apoA-I molecular weight with a 1.9 nm blue shift of the maximum wavelength fluorescence than rHDL alone (rHDL-0). Other rHDLs containing Chinese policosanols (rHDL-2, rHDL-3, and rHDL-4) showed similar particle sizes with an rHDL-0 and 1.1–1.3 nm blue shift of wavelength maximum fluorescence (WMF). Among all rHDLs, the rHDL-1 showed the strongest antioxidant ability to inhibit cupric ion-mediated LDL oxidation. The rHDL-1-treated LDL showed the most distinct band intensity and particle morphology compared with the other rHDLs. The rHDL-1 also exerted the highest anti-glycation activity to inhibit the fructose-mediated glycation of human HDL₂ with the protection of apoA-I from proteolytic degradation. At the same time, other rHDLs showed a loss of anti-glycation activity with severe degradation. A microinjection of each rHDL alone showed that rHDL-1 had the highest survivability of approximately 85 ± 3%, with the fastest developmental speed and morphology. In contrast, rHDL-3 showed the lowest survivability, around 71 ± 5%, with the slowest developmental speed. A microinjection of carboxymethyllysine (CML), a pro-inflammatory advanced glycated end product, into zebrafish embryos resulted in severe embryo death of approximately 30 ± 3% and developmental defects with the slowest developmental speed. On the other hand, the phosphate buffered saline (PBS)-injected embryo showed 83 ± 3% survivability. A co-injection of CML and each rHDL into adult zebrafish showed that rHDL-1 (Cuban policosanol) induced the highest survivability, around 85 ± 3%, while rHDL-0 showed 67 ± 7% survivability. In addition, rHDL-2, rHDL-3, and rHDL-4 showed 67 ± 5%, 62 ± 37, and 71 ± 6% survivability, respectively, with a slower developmental speed and morphology. In conclusion, Cuban policosanol showed the strongest ability to form rHDLs with the most distinct morphology and the largest size. The rHDL-containing Cuban policosanol (rHDL-1) showed the strongest antioxidant ability against LDL oxidation, anti-glycation activity to protect apoA-I from degradation, and the highest anti-inflammatory activity to protect embryo death under the presence of CML. Full article

(This article belongs to the Special Issue Quality of HDL and LDL: Metabolism, Nutrition, Exercise and Health Impact 2.0)

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