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Patients with Rheumatoid Arthritis Show Altered Lipoprotein Profiles with Dysfunctional High-Density Lipoproteins that Can Exacerbate Inflammatory and Atherogenic Process.

  • Jae-Yong Kim‎ et al.
  • PloS one‎
  • 2016‎

In order to identify putative biomarkers in lipoprotein, we compared lipid and lipoprotein properties between rheumatoid arthritis (RA) patients and control with similar age.


High Consumption of Iron Exacerbates Hyperlipidemia, Atherosclerosis, and Female Sterility in Zebrafish via Acceleration of Glycation and Degradation of Serum Lipoproteins.

  • So-Hee Kim‎ et al.
  • Nutrients‎
  • 2017‎

Elevated serum iron level is linked with an increased risk of diabetes and atherosclerosis. However, the pathological mechanism by which iron affects serum lipoprotein levels is unknown. To elucidate the mechanism, a high dose of ferrous ion was applied (final 60 µM, 120 µM) to human serum lipoproteins, macrophages, and human dermal fibroblast (HDF) cells. Iron-treated lipoproteins showed loss of antioxidant ability along with protein degradation and multimerization, especially co-treatment with fructose (final 10 mM). In the presence of fructose, HDF cells showed 3.5-fold more severe cellular senescence, as compared to the control, dependent on the dosage of fructose. In macrophages, phagocytosis of acetylated low-density lipoprotein (acLDL) was more accelerated by ferrous ion, occurring at a rate that was up to 1.8-fold higher, than acLDL alone. After 24 weeks supplementation with 0.05% and 0.1% ferrous ion in the diet (wt/wt), serum total cholesterol (TC) level was elevated 3.7- and 2.1-fold, respectively, under normal diet (ND). Serum triglyceride (TG) was elevated 1.4- and 1.7-fold, respectively, under ND upon 0.05% and 0.1% ferrous ion supplementation. Serum glucose level was elevated 2.4- and 1.2-fold under ND and high cholesterol diet (HCD), respectively. However, body weight was decreased by the Fe2+ consumption. Iron consumption caused severe reduction of embryo laying and reproduction ability, especially in female zebrafish via impairment of follicular development. In conclusion, ferrous ion treatment caused more pro-atherogenic, and pro-senescence processes in human macrophages and dermal cells. High consumption of iron exacerbated hyperlipidemia and hyperglycemia as well as induced fatty liver changes and sterility along with reduction of female fertility.


Native High-Density Lipoproteins (HDL) with Higher Paraoxonase Exerts a Potent Antiviral Effect against SARS-CoV-2 (COVID-19), While Glycated HDL Lost the Antiviral Activity.

  • Kyung-Hyun Cho‎ et al.
  • Antioxidants (Basel, Switzerland)‎
  • 2021‎

Human high-density lipoproteins (HDL) show a broad spectrum of antiviral activity in terms of anti-infection. Although many reports have pointed out a correlation between a lower serum HDL-C and a higher risk of COVID-19 infection and progression, the in vitro antiviral activity of HDL against SARS-CoV-2 has not been reported. HDL functionality, such as antioxidant and anti-infection, can be impaired by oxidation and glycation and a change to pro-inflammatory properties. This study compared the antiviral activity of native HDL with glycated HDL via fructosylation and native low-density lipoproteins (LDL). After 72 h of fructosylation, glycated HDL showed a typical multimerized protein pattern with an elevation of yellowish fluorescence. Glycated HDL showed a smaller particle size with an ambiguous shape and a loss of paraoxonase activity up to 51% compared to native HDL. The phagocytosis of acetylated LDL was accelerated 1.3-fold by glycated HDL than native HDL. Native HDL showed 1.7 times higher cell viability and 3.6 times higher cytopathic effect (CPE) inhibition activity against SARS-CoV-2 than that of glycated HDL under 60 μg/mL (approximately final 2.2 μM) in a Vero E6 cell. Native HDL showed EC50 = 52.1 ± 1.1 μg/mL (approximately final 1.8 μM) for the CPE and CC50 = 79.4 ± 1.5 μg/mL (around 2.8 μM). The selective index (SI) of native HDL was calculated to be 1.52. In conclusion, native HDL shows potent antiviral activity against SARS-CoV-2 without cytotoxicity, while the glycation of HDL impairs its antiviral activity. These results may explain why patients with diabetes mellitus or hypertension are more sensitive to a COVID-19 infection and have a higher risk of mortality.


Cuban Sugar Cane Wax Acid and Policosanol Showed Similar Atheroprotective Effects with Inhibition of LDL Oxidation and Cholesteryl Ester Transfer via Enhancement of High-Density Lipoproteins Functionality.

  • Kyung-Hyun Cho‎ et al.
  • Cardiovascular therapeutics‎
  • 2019‎

Cuban sugarcane wax acids (SCWA) and policosanol (PCO) are mixtures of higher aliphatic acids and alcohols, respectively, purified from sugarcane wax with different chief components. Although it has been known that they have antioxidant and anti-inflammatory activities, physiological properties on molecular mechanism of SCWA have been less studied than PCO.


Decrease in Serum HDL-C Level Is Associated with Elevation of Blood Pressure: Correlation Analysis from the Korean National Health and Nutrition Examination Survey 2017.

  • Kyung-Hyun Cho‎ et al.
  • International journal of environmental research and public health‎
  • 2020‎

A low-serum, high-density lipoproteins-cholesterol (HDL-C) level and high blood pressure (BP) are independent risk factors for cardiovascular disease and dementia. In the present study, in order to find putative correlation between low HDL-C and hypertension, 4552 subjects (20-80 years old) were selected from the Korean National Health And Nutrition Examination Survey 2017 (KNHANES VII-2, n = 2017 men, n = 2535 women). They were classified into four levels of blood pressure, ranging from BP1 (normal, below 120/80 mmHg for systolic BP (SBP)/diastolic BP (DBP), BP2 (prehypertension, 120/80 to 139/89 mmHg), BP3 (hypertension stage 1, 140/90-159/99 mmHg), and BP4 (hypertension stage 2, higher than 160/100 mmHg). Generally, in the total population, a higher SBP level and age were associated with a lower HDL-C in both genders. However, DBP was not associated with age in men. In the total population, Pearson's correlation analysis revealed that SBP (r = -0.188, p < 0.001) and DBP (r = -0.198, p < 0.001) showed negative correlations with percentage of HDL-C in total cholesterol (TC), HDL-C/TC (%). In both genders, HDL-C gradually decreased with age and HDL-C/TC (%) was more accurate in expressing a correlation with BP. Women showed a more distinct decrease in HDL-C with an elevation of BP and age than men. Both elevation of DBP and SBP were associated with a decrease in HDL-C, around 2.3-2.4 mg/dL, between normal range and hypertension 2 stage. Additionally, DBP was significantly associated with HDL-C/TC (%) (men: r = -0.136, p < 0.001; women: r = -0.152, p < 0.001), while HDL-C did not show a significant association with a change in DBP. In conclusion, SBP was positively correlated with age, but DBP did not change significantly with age. The correlation of BP and HDL-C depending on age showed that SBP gradually increased and HDL-C decreased with an increase in age. The percentage of HDL-C in TC was more significantly associated with a change in SBP and DBP in both genders.


Rapid Decrease in HDL-C in the Puberty Period of Boys Associated with an Elevation of Blood Pressure and Dyslipidemia in Korean Teenagers: An Explanation of Why and When Men Have Lower HDL-C Levels Than Women.

  • Kyung-Hyun Cho‎ et al.
  • Medical sciences (Basel, Switzerland)‎
  • 2021‎

Low serum high-density lipoproteins-cholesterol (HDL-C) levels and high blood pressure are linked to each other and are recognized as independent risk factors of cardiovascular disease and dementia. HDL can cross the blood-brain barrier to remove amyloid plaque and the blood-testis barrier to supply cholesterol for spermatogenesis, but LDL cannot. During the teenage period, between 10 and 19 years of age, the systolic blood pressure (BP) increased gradually to 7.9% in boys (p < 0.001), but not in girls (p = 0.141). The boys' group showed a remarkable decrease in the total cholesterol (TC) and HDL-C from 10 to 15 years of age (p < 0.001). After then, the TC level increased again at 19 years of age to the previous level (p < 0.001). On the other hand, the HDL-C level at 19 years of age in the boys' group was not restored to the previous level at 10 years of age. The girls' group maintained similar TC (p < 0.001) and HDL-C (p < 0.001) levels from 10 to 19 years of age. These results suggest there was a remarkable difference in cholesterol consumption, particularly in the HDL-C level between boys and girls during the pubertal period. Correlation analysis showed an inverse association between the HDL-C level and SBP in boys (r = -0.133, p < 0.001) and girls (r = -0.065, p = 0.009) from 10 to 19 years of age. Interestingly, only the boys' group showed an inverse association with the diastolic BP (r = -0.122, p < 0.001); the girls' group did not have such an association (r = -0.016, p = 0.516). In conclusion, the boys' group showed a sharp decrease in the HDL-C level from 10 to 15 years of age, whereas the girls' group showed an increase in the HDL-C level during the same period. These results explain why men have a lower serum HDL-C level than women in adulthood.


Slim Body Weight Is Highly Associated With Enhanced Lipoprotein Functionality, Higher HDL-C, and Large HDL Particle Size in Young Women.

  • Ki-Hoon Park‎ et al.
  • Frontiers in endocrinology‎
  • 2018‎

There has been no information about the correlations between body weight distribution and lipoprotein metabolism in terms of high-density lipoproteins-cholesterol (HDL-C) and cholesteryl ester transfer protein (CETP). In this study, we analyzed the quantity and quality of HDL correlations in young women (21.5 ± 1.2-years-old) with a slim (n = 21, 46.2 ± 3.8 kg) or plump (n = 30, 54.6 ± 4.4 kg) body weight. Body weight was inversely correlated with the percentage of HDL-C in total cholesterol (TC). The plump group showed 40% higher body fat (26 ± 3 %) and 86% more visceral fat mass (VFM, 1.3 ± 0.3 kg) than the slim group, which showed 18 ± 2% body fat and 0.7 ± 0.2 kg of VFM. Additionally, the plump group showed 20% higher TC, 58% higher triglyceride (TG), and 12% lower HDL-C levels in serum. The slim group showed 34% higher apoA-I but 15% lower CETP content in serum compared to the plump group. The slim group showed a 13% increase in particle size and 1.9-fold increase in particle number with enhanced cholesterol efflux activity. Although the plump group was within a normal body mass index (BMI) range, its lipid profile and lipoprotein properties were distinctly different from those of the slim group in terms of CETP mass and activity, HDL functionality, and HDL particle size.


Short-Term Consumption of Cuban Policosanol Lowers Aortic and Peripheral Blood Pressure and Ameliorates Serum Lipid Parameters in Healthy Korean Participants: Randomized, Double-Blinded, and Placebo-Controlled Study.

  • Hye-Jeong Park‎ et al.
  • International journal of environmental research and public health‎
  • 2019‎

The current study was designed to investigate the short-term effects of policosanol consumption on blood pressure (BP) and the lipid parameters in healthy Korean participants with prehypertension. A total of 84 healthy participants were randomly allocated to three groups receiving placebo, 10 mg of policosanol, or 20 mg of policosanol for 12 weeks. Based on an average of three measurements of peripheral BP, the policosanol 20 mg group exhibited the most significant reduction, that is, up to 7.7% reduction of average systolic BP (SBP) from 136.3 ± 6.1 mmHg (week 0) to 125.9 ± 8.6 mmHg (week 12, p < 0.001). Between group comparisons using repeated measures ANOVA showed that the policosanol 20 mg group had a significant reduction of SBP at 12 weeks (p = 0.020) and a reduction of diastolic BP (DBP) at 8 weeks (p = 0.041) and 12 weeks (p = 0.035). The policosanol 10 mg and 20 mg groups showed significant reductions in aortic SBP of 7.4% and 8.3%, respectively. The policosanol groups showed significant reductions of total cholesterol (TC) of 9.6% and 8.6% and low-density lipoproteins (LDL-C) of 21% and 18% for 10 mg and 20 mg of policosanol, respectively. Between group comparisons using repeated measures ANOVA showed that the policosanol (10 mg and 20 mg) groups at 12 weeks had a significant reduction of TC (p = 0.0004 and p = 0.001) and LDL-C (p = 0.00005 and p = 0.0001) and elevation of %HDL-C (p = 0.048 and p = 0.014). In conclusion, 12-week consumption of policosanol resulted in significant reductions of peripheral SBP and DBP, aortic SBP and DBP, mean arterial pressure (MAP), and serum TC and LDL-C with elevation of % HDL-C.


Consumption of policosanol enhances HDL functionality via CETP inhibition and reduces blood pressure and visceral fat in young and middle-aged subjects.

  • Jae-Yong Kim‎ et al.
  • International journal of molecular medicine‎
  • 2017‎

It is well-known that policosanol can improve serum lipid profiles, although the physiological mechanism is still unknown. Here, we investigated functional and structural changes in lipoproteins after consumption of policosanol. To investigate the physiological effect of policosanol, we analyzed serum parameters in young non-smoker (YN; n=7, 24.0±2.4 years), young smoker (YS; n=7, 26.3±1.5 years), and middle-aged subjects (MN; n=11, 52.5±9.8 years) who consumed policosanol daily (10 mg/day) for 8 weeks. After 8 weeks, systolic blood pressure was significantly lowered to 4% (7 mmHg, p=0.022) from initial levels in the YS and MN groups. Moisture content of facial skin increased up to 38 and 18% from initial levels in the YS and MN groups, respectively. Serum triglyceride (TG) levels decreased to 28 and 26% from initial levels in the YN and MN groups, respectively. The percentage of high-density lipoprotein-cholesterol (HDL-C) in total cholesterol was elevated in all subjects (YN, 36%; YS, 35%; MN, 8%) after 8 weeks of policosanol consumption. All groups showed a reduction in serum glucose and uric acid levels. Serum cholesteryl ester transfer protein (CETP) activity was significantly diminished up to 21 and 32% from initial levels in the YN and MN groups, respectively. After 8 weeks, oxidation of the low-density lipoprotein fraction was markedly reduced accompanied by decreased apolipoprotein B (apoB) fragmentation. In the HDL fraction, paraoxonase activity was elevated by 17% along with elevation of apoA-I and cholesterol contents. Electron microscopy revealed that the size and number of HDL particles increased after 8 weeks, and the YS group showed a 2-fold increase in particle size. Daily consumption of policosanol for 8 weeks resulted in lowered blood pressure, reduced serum TG level and CETP activity, and elevated HDL-C contents. These functional enhancements of HDL can prevent and/or attenuate aging-related diseases, hypertension, diabetes and coronary heart disease.


Decrease in HDL-C is Associated with Age and Household Income in Adults from the Korean National Health and Nutrition Examination Survey 2017: Correlation Analysis of Low HDL-C and Poverty.

  • Kyung-Hyun Cho‎ et al.
  • International journal of environmental research and public health‎
  • 2019‎

A low serum high-density lipoproteins-cholesterol (HDL-C) level is a risk factor of cardiovascular disease and dementia. On the other hand, no study has elucidated the correlation between household income and the HDL-C level in the adult population. In the present study, 5535 subjects (20-80 year-old individuals) were selected from the Korean national health and nutrition examination survey 2017 (KNHANES VII-2, n = 2469 men, n = 3066 women). They were classified into five levels of household income grades ranging from one (the lowest) to five (the highest). They were also classified according to the HDL-C level: category 1 (<40 mg/dL, n = 943), category 2 (40-49 mg/dL, n = 1764), category 3 (50-59 mg/dL, n = 1572), category 4 (60-69 mg/dL, n = 820), and category 5 (≥70 mg/dL, n = 436). Generally, in both genders, a higher HDL-C level is associated with a larger percentage of income grades 4 and 5. Moreover, the lowest HDL-C group showed the largest percentage of income grade 1. In both groups, a significant increase in the average income grade was associated with a concomitant increase in the HDL-C level (men, p = 0.03, women, p < 0.001). In the low HDL-C category, a lower income grade is associated directly with a lower HDL-C level, which suggests that poverty is associated directly with a low HDL-C. Women showed a 3.3-fold higher incidence of dementia than men did at later-life. The sharp decrease in HDL-C in the female group older than 50 was accompanied by a dramatic increase in the incidence of dementia. However, the male group showed a relatively mild decrease in the HDL-C level after mid-life and weak elevation in the incidence of dementia. In conclusion, in both genders, the lower income group showed a larger prevalence of low-HDL-C levels. The decrease in HDL-C after middle age was strongly associated with the considerable increase in dementia in later-life.


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