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Biomolecules
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Lipids in Atherosclerosis
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Lipids in Atherosclerosis

A special issue of Biomolecules (ISSN 2218-273X). This special issue belongs to the section "Biomacromolecules: Lipids".

Deadline for manuscript submissions: closed (20 November 2023) | Viewed by 15442

Special Issue Editor

Prof. Dr. Yoshinari Uehara

E-Mail Website
Guest Editor
Faculty of Sports and Health Science, Fukuoka University, Fukuoka 814-0180, Japan
Interests: atherosclerosis; HDL; lipid metabolism; sports medicine; function of skeletal muscle
Special Issues, Collections and Topics in MDPI journals

Special Issue Information

Dear Colleagues,

Cardiovascular diseases, such as myocardial infarction, are caused by atherosclerotic plaques in coronary arteries, and the occurrence of such diseases increases with the elevation of plasma low-density lipoprotein (LDL) cholesterol levels. Many clinical studies that used HMG-CoA reductase and PCSK9 inhibitors have also shown that LDL-cholesterol-reducing therapy contributes to a reduction in cardiovascular disease risk. On the contrary, many cases have relatively low LDL cholesterol levels or accelerated atherosclerotic plaque formation even with LDL-cholesterol-lowering therapy, and factors other than LDL cholesterol have been proposed. Therefore, the progression of atherosclerotic plaque formation is not only related to the amount of cholesterol in lipoproteins but also the deterioration of lipoprotein quality. In this Special Issue, we introduce and discuss innovative risks of atherosclerotic plaque formation in addition to the therapeutic applications of various factors “beyond LDL cholesterol”, such as high-density lipoprotein, triglyceride-rich lipoproteins, the particle size and number of lipoproteins, and modified lipoproteins.

Prof. Dr. Yoshinari Uehara
Guest Editor

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Keywords

  • low-density lipoprotein
  • high-density lipoprotein
  • triglyceride-rich lipoprotein
  • apolipoprotein
  • physical activity and lipoproteins

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Published Papers (6 papers)

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Research

Jump to: Review

18 pages, 11367 KiB  
Article
Associations of High-Density Lipoprotein Functionality with Coronary Plaque Characteristics in Diabetic Patients with Coronary Artery Disease: Integrated Backscatter Intravascular Ultrasound Analysis
by Kohei Takata, Satoshi Imaizumi, Atsushi Iwata, Bo Zhang, Emi Kawachi, Shin-ichiro Miura and Masahiro Ogawa
Biomolecules 2023, 13(9), 1278; https://doi.org/10.3390/biom13091278 - 22 Aug 2023
Cited by 2 | Viewed by 1220
Abstract
High-density lipoprotein (HDL) functionality has been reported to be associated with coronary artery disease (CAD). However, little is known about the impact of HDL functionality on coronary atherosclerosis. Thirty-eight type 2 diabetic patients with CAD who underwent percutaneous coronary intervention were examined. Coronary [...] Read more.
High-density lipoprotein (HDL) functionality has been reported to be associated with coronary artery disease (CAD). However, little is known about the impact of HDL functionality on coronary atherosclerosis. Thirty-eight type 2 diabetic patients with CAD who underwent percutaneous coronary intervention were examined. Coronary atheroma burden and plaque composition of the culprit lesions were assessed using conventional gray-scale and integrated backscatter intravascular ultrasound. HDL-mediated cholesterol efflux capacity (HDL-CEC) and HDL antioxidant capacity, estimated as HDL inflammatory index (HII), were examined. The associations between HDL functionality and coronary plaques were analyzed using multivariate data analysis, including principal components analysis and orthogonal partial least squares (OPLS) models. Percent atheroma volume was correlated with HDL-CEC (r = 0.34, p = 0.04) but not with HII (p = 0.65). The OPLS model demonstrated that the percentage lipid volume was significantly associated with HDL functionality [coefficient (95% confidence interval); HDL-CEC: −0.26 (−0.49, −0.04); HII: 0.34 (0.08, 2.60), respectively]. HII exhibited the highest variable importance in projection score, indicating the greatest contribution. HDL functionality was associated with coronary plaque composition, a key component of plaque vulnerability. Our findings highlight the potential importance of HDL functionality for coronary plaque stabilization. Full article
(This article belongs to the Special Issue Lipids in Atherosclerosis)
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20 pages, 4458 KiB  
Article
Altered Distribution of Unesterified Cholesterol among Lipoprotein Subfractions of Patients with Diabetes Mellitus Type 2
by Livia Noemi Kolb, Alaa Othman, Lucia Rohrer, Jan Krützfeldt and Arnold von Eckardstein
Biomolecules 2023, 13(3), 497; https://doi.org/10.3390/biom13030497 - 8 Mar 2023
Cited by 2 | Viewed by 2118
Abstract
Biomarkers are important tools to improve the early detection of patients at high risk for developing diabetes as well as the stratification of diabetic patients towards risks of complications. In addition to clinical variables, we analyzed 155 metabolic parameters in plasma samples of [...] Read more.
Biomarkers are important tools to improve the early detection of patients at high risk for developing diabetes as well as the stratification of diabetic patients towards risks of complications. In addition to clinical variables, we analyzed 155 metabolic parameters in plasma samples of 51 healthy volunteers and 66 patients with diabetes using nuclear magnetic resonance (NMR) spectrometry. Upon elastic net analysis with lasso regression, we confirmed the independent associations of diabetes with branched-chain amino acids and lactate (both positive) as well as linoleic acid in plasma and HDL diameter (both inverse). In addition, we found the presence of diabetes independently associated with lower concentrations of free cholesterol in plasma but higher concentrations of free cholesterol in small HDL. Compared to plasmas of non-diabetic controls, plasmas of diabetic subjects contained lower absolute and relative concentrations of free cholesterol in all LDL and HDL subclasses except small HDL but higher absolute and relative concentrations of free cholesterol in all VLDL subclasses (except very small VLDL). These disbalances may reflect disturbances in the transfer of free cholesterol from VLDL to HDL during lipolysis and in the transfer of cell-derived cholesterol from small HDL via larger HDL to LDL. Full article
(This article belongs to the Special Issue Lipids in Atherosclerosis)
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15 pages, 585 KiB  
Article
Significance of Circulating Remnant Lipoprotein Cholesterol Levels Measured by Homogeneous Assay in Patients with Type 2 Diabetes
by Kazumi Matsushima-Nagata, Takeshi Matsumura, Yuki Kondo, Kensaku Anraku, Kazuki Fukuda, Mikihiro Yamanaka, Masahiro Manabe, Tetsumi Irie, Eiichi Araki and Hiroyuki Sugiuchi
Biomolecules 2023, 13(3), 468; https://doi.org/10.3390/biom13030468 - 3 Mar 2023
Cited by 1 | Viewed by 1815
Abstract
Remnant lipoproteins (RLs), which are typically present at high concentrations in patients with type 2 diabetes mellitus (T2DM), are associated with cardiovascular disease (CVD). Although an RL cholesterol homogeneous assay (RemL-C) is available for the measurement of RL concentrations, there have been no [...] Read more.
Remnant lipoproteins (RLs), which are typically present at high concentrations in patients with type 2 diabetes mellitus (T2DM), are associated with cardiovascular disease (CVD). Although an RL cholesterol homogeneous assay (RemL-C) is available for the measurement of RL concentrations, there have been no studies of the relationship between RemL-C and clinical parameters in T2DM. Therefore, we evaluated the relationships between RemL-C and CVD-related parameters in patients with T2DM. We performed a cross-sectional study of 169 patients with T2DM who were hospitalized at Kumamoto University Hospital. Compared with those with low RemL-C, those with higher RemL-C had higher fasting plasma glucose, homeostasis model assessment for insulin resistance (HOMA-R), total cholesterol, triglyceride, small dense low-density lipoprotein cholesterol (sdLDL-C), and urinary albumin-creatinine ratio; and lower high-density lipoprotein cholesterol, adiponectin, and ankle brachial pressure index (ABI). Multivariate logistic regression analysis showed that sdLDL-C and ABI were significantly and independently associated with high RemL-C. Although LDL-C was lower in participants with CVD, there was no difference in RemL-C between participants with or without CVD. Thus, RemL-C may represent a useful index of lipid and glucose metabolism, and that may be a marker of peripheral atherosclerotic disease (PAD) in male patients with T2DM. Full article
(This article belongs to the Special Issue Lipids in Atherosclerosis)
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11 pages, 2349 KiB  
Article
Dipeptidyl Peptidase-4 Inhibitor Sitagliptin Phosphate Accelerates Cellular Cholesterol Efflux in THP-1 Cells
by Tomohiro Komatsu, Satomi Abe, Shihoko Nakashima, Kei Sasaki, Yasuki Higaki, Keijiro Saku, Shin-ichiro Miura and Yoshinari Uehara
Biomolecules 2023, 13(2), 228; https://doi.org/10.3390/biom13020228 - 24 Jan 2023
Cited by 4 | Viewed by 2329
Abstract
Cholesterol efflux is a major atheroprotective function of high-density lipoproteins (HDLs) which removes cholesterol from the foam cells of lipid-rich plaques in Type 2 diabetes. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin phosphate increases plasma glucagon-like peptide-1 (GLP-1) concentrations and is used to treat [...] Read more.
Cholesterol efflux is a major atheroprotective function of high-density lipoproteins (HDLs) which removes cholesterol from the foam cells of lipid-rich plaques in Type 2 diabetes. The dipeptidyl peptidase-4 (DPP-4) inhibitor sitagliptin phosphate increases plasma glucagon-like peptide-1 (GLP-1) concentrations and is used to treat Type 2 diabetes. GLP-1 plays an important role in regulating insulin secretion and expression via the GLP-1 receptor (GLP-1R), which is expressed in pancreatic islets as well as freshly isolated human monocytes and THP-1 cells. Here, we identified a direct role of GLP-1 and DPP-4 inhibition in HDL function. Cholesterol efflux was measured in cultivated phorbol 12-myristate 13-acetate-treated THP-1 cells radiolabeled with 3H-cholesterol and stimulated with liver X receptor/retinoid X receptor agonists. Contrary to vildagliptin, sitagliptin phosphate together with GLP-1 significantly (p < 0.01) elevated apolipoprotein (apo)A1-mediated cholesterol efflux in a dose-dependent manner. The sitagliptin-induced increase in cholesterol efflux did not occur in the absence of GLP-1. In contrast, adenosine triphosphate-binding cassette transporter A1 (ABCA1) mRNA and protein expressions in the whole cell fraction were not changed by sitagliptin in the presence of GLP-1, although sitagliptin treatment significantly increased ABCA1 protein expression in the membrane fraction. Furthermore, the sitagliptin-induced, elevated efflux in the presence of GLP-1 was significantly decreased by a GLP-1R antagonist, an effect that was not observed with a protein kinase A inhibitor. To our knowledge, the present study reports for the first time that sitagliptin elevates cholesterol efflux in cultivated macrophages and may exert anti-atherosclerotic actions that are independent of improvements in glucose metabolism. Our results suggest that sitagliptin enhances HDL function by inducing a de novo HDL synthesis via cholesterol efflux. Full article
(This article belongs to the Special Issue Lipids in Atherosclerosis)
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16 pages, 2514 KiB  
Article
Beeswax Alcohol and Fermented Black Rice Bran Synergistically Ameliorated Hepatic Injury and Dyslipidemia to Exert Antioxidant and Anti-Inflammatory Activity in Ethanol-Supplemented Zebrafish
by Youngji Han, Seonggeun Zee and Kyung-Hyun Cho
Biomolecules 2023, 13(1), 136; https://doi.org/10.3390/biom13010136 - 9 Jan 2023
Cited by 3 | Viewed by 2441
Abstract
Alcohol abuse, a global health problem, is closely associated with many pathological processes, such as dyslipidemia and cardiovascular disease. In particular, excessive alcohol consumption promotes dyslipidemia and liver damage, such as hepatic steatosis, fibrosis, and cirrhosis. Beeswax alcohol (BWA) is a natural product [...] Read more.
Alcohol abuse, a global health problem, is closely associated with many pathological processes, such as dyslipidemia and cardiovascular disease. In particular, excessive alcohol consumption promotes dyslipidemia and liver damage, such as hepatic steatosis, fibrosis, and cirrhosis. Beeswax alcohol (BWA) is a natural product used for its antioxidant properties that has not been evaluated for its efficacy in alcohol-induced liver injury. In the present study, zebrafish were exposed to 1% ethanol with supplementation of 10% fermented black rice bran (BRB-F), 10% BWA, or 10% mixtures of BWA+BRB-F (MIX). The BRB-F, BWA, and MIX supplementation increased the survival rate dramatically without affecting the body weight changes. In histology of hepatic tissue, alcoholic foamy degeneration was ameliorated by the BWA or MIX supplements. Moreover, dihydroethidium (DHE) and immunohistochemistry staining suggested that the MIX supplement decreased the hepatic ROS production and interleukin-6 expression significantly owing to the enhanced antioxidant properties, such as paraoxonase. Furthermore, the MIX supplement improved alcohol-induced dyslipidemia and oxidative stress. The BWA and MIX groups showed lower blood total cholesterol (TC) and triglyceride (TG) levels with higher high-density lipoprotein-cholesterol (HDL-C) than the alcohol-alone group. The MIX group showed the highest HDL-C/TC ratio and HDL-C/TG ratio with the lowest low-density lipoprotein (LDL)-C/HDL-C ratio. In conclusion, BWA and BRB-F showed efficacy to treat alcohol-related metabolic disorders, but the MIX supplement was more effective in ameliorating the liver damage and dyslipidemia, which agrees with an enhanced antioxidant and anti-inflammatory activity exhibited by BWA/BRB-F in a synergistic manner. Full article
(This article belongs to the Special Issue Lipids in Atherosclerosis)
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Review

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16 pages, 596 KiB  
Review
HDL Functions—Current Status and Future Perspectives
by Yasuhiro Endo, Masanori Fujita and Katsunori Ikewaki
Biomolecules 2023, 13(1), 105; https://doi.org/10.3390/biom13010105 - 4 Jan 2023
Cited by 22 | Viewed by 4495
Abstract
Cardiovascular disease (CVD) is the leading cause of death in Western countries. A low HDL-C is associated with the development of CVD. However, recent epidemiology studies have shown U-shaped curves between HDL-C and CVD mortality, with paradoxically increased CVD mortality in patients with [...] Read more.
Cardiovascular disease (CVD) is the leading cause of death in Western countries. A low HDL-C is associated with the development of CVD. However, recent epidemiology studies have shown U-shaped curves between HDL-C and CVD mortality, with paradoxically increased CVD mortality in patients with extremely high HDL-C levels. Furthermore, HDL-C raising therapy using nicotinic acids or CETP inhibitors mostly failed to reduce CVD events. Based on this background, HDL functions rather than HDL-C could be a novel biomarker; research on the clinical utility of HDL functionality is ongoing. In this review, we summarize the current status of HDL functions and their future perspectives from the findings of basic research and clinical trials. Full article
(This article belongs to the Special Issue Lipids in Atherosclerosis)
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