Oxidized high-density lipoprotein is associated with increased plasma glucose in non-diabetic dyslipidemic subjects

Kotani, Kazuhiko; Sakane, Naoki; Ueda, Masashi; Mashiba, Shinichi; Hayase, Yasuyuki; Tsuzaki, Kokoro; Yamada, Toshiyuki; Remaley, Alan T.

doi:10.1016/j.cca.2012.08.021

Cited by 17 publications

(18 citation statements)

References 46 publications

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“…Plasma levels of ox-HDL in T2DM patients were reported to be higher than those in healthy individuals [138]. It was found that ox-HDL is independently and positively correlated with fasting glucose levels, suggesting that high glucose levels may also contribute to HDL oxidation [139]. Glycated HDL is more susceptible to oxidation in vitro as shown by an increase in lipid peroxidation products and thiobarbituric acid-reactive substances (TBARS) following incubation of HDL with glucose.…”

Section: Abnormal Hdl In Diabetes Mellitusmentioning

confidence: 99%

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

Liu¹

2020

Apolipoproteins, Triglycerides and Cholesterol

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High-density lipoprotein (HDL) is a heterogeneous particle composed of apolipoproteins, enzymes, and lipids. Besides transporting cholesterol to the liver, HDL also exerts many protections on anti-oxidation, anti-inflammation, and anti-apoptosis. Initial understandings of HDL came from its protective roles against atherosclerosis and the observation that high plasma HDL cholesterol (HDL-C) levels seemed to decrease cardiovascular disease (CVD) attack. However, those patients either with cholesterol ester transfer protein (CETP) deficiency or taking CETP inhibitors substantially elevated HDL-C levels but did not necessarily decrease CVD risk. Thus, some researchers suggested that quantitative measurements of HDL particle (HDL-P) might be more valuable than traditional HDL-C measurements. What is more bewildering is that HDL from patients with systemic inflammation decreased its protective effects and even became a pro-inflammatory factor. Recently, synthesized HDL and apolipoprotein mimetic peptides showed biological functions similar to native ones. Expectedly, lots of novel measurement methods and therapeutic agents about HDL would be established soon.

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Section: Abnormal Hdl In Diabetes Mellitusmentioning

confidence: 99%

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

Liu¹

2020

Apolipoproteins, Triglycerides and Cholesterol

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“…HDL is susceptible to oxidative modification under certain circumstances, such as in diabetes (27), metabolic syndrome, and cardiovascular diseases (28,29). To further clarify the pathophysiologic significance of oxidative modification of HDL in clinical diseases, we isolated HDL from MS patients and investigated its effects on oxidative stress and CHOP-mediated apoptosis in RAW264.7 macrophages.…”

Section: Hdl From Ms Patients Induces Oxidative Stress and Chop-mediamentioning

confidence: 99%

“…Thus, the effects of modification of HDL and changes in HDL composition on HDL properties and pathological significance drew great attention from researchers. As the most common type of modification under certain circumstances, such as in diabetes (27), metabolic syndrome, and cardiovascular diseases (28,29,38), oxidation was shown to significantly affect the biological properties of HDL from many aspects, including altering paraoxonase structure and decreasing lactonase activity (39), which might cause HDL dysfunction, as assessed by decreased antiatherogenic abilities or even becoming proatherogenic (6). For example, ox-HDL has been shown to halt cholesterol efflux from foam cells in comparison with native HDL (5).…”

Section: Hdl From Ms Patients Induces Oxidative Stress and Chop-mediamentioning

confidence: 99%

“…Similar results were obtained in the TLR4 antibody-pretreated macrophages, further suggesting that TLR4 may mediate ox-HDL-induced oxidative stress and subsequent activation of a CHOP-induced apoptotic pathway in macrophages. HDL is susceptible to structural modification, including oxidation and glycation under certain circumstances such as diabetes, MS, and atherosclerosis, and loses its antiatherogenic abilities or even becomes proatherogenic (27)(28)(29)38). To further confirm the clinical significance of HDL modification, we explored the inductive effect of HDL isolated from MS patients on oxidative stress and the CHOPmediated apoptotic pathway in macrophages.…”

Section: Hdl From Ms Patients Induces Oxidative Stress and Chop-mediamentioning

confidence: 99%

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Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway

Yao¹,

Tian²,

Zhao³

et al. 2017

Journal of Lipid Research

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This article is available online at http://www.jlr.org Atherosclerosis, one of the prime causes of heart attack and stroke, has been well known as a lipid-driven inflammatory disease characterized by macrophage accumulation in subendothelial space. Apoptosis of macrophage-derived foam cells, especially in advanced atherosclerotic lesions where phagocytic clearance of dead and dying cells is defective, results in acellular necrotic lesions that are prone to plaque rupture and thrombosis formation, leading to the majority of acute vascular events (1). Thus, deeper understanding of the mechanisms of macrophage apoptosis may pave the way for developing novel therapeutic strategies to effectively prevent atherosclerotic plaque rupture and subsequent clinical complications (2). Oxidized LDL (ox-LDL) has been recognized as a major inducer, promoting foam cell formation and apoptosis in macrophages (3). In contrast, HDL exerts antiatherogenic functions such as promoting reverse cholesterol transport, suppressing inflammation, inhibiting LDL oxidation, and increasing endothelial nitric oxide production (4). However, accumulating evidence suggests that HDL, like LDL, is also susceptible to oxidative modification. Oxidized HDL Abstract Oxidized HDL (ox-HDL), unlike native HDL that exerts antiatherogenic effects, plays a proatherogenic role. However, the underlying mechanisms are not completely understood. This study was designed to explore the inductive effect of ox-HDL on endoplasmic reticulum (ER) stress-CCAAT-enhancer-binding protein homologous protein (CHOP)-mediated macrophage apoptosis and its upstream mechanisms. Our results showed that ox-HDL could be ingested by macrophages, causing intracellular lipid accumulation. As with tunicamycin (an ER stress inducer), ox-HDL induced macrophage apoptosis with concomitant activation of ER stress pathway, including nuclear translocation of activating transcription factor 6, phosphorylation of protein kinase-like ER kinase and eukaryotic translation initiation factor 2, and upregulation of glucose-regulated protein 78 and CHOP, which were inhibited by 4-phenylbutyric acid (PBA, an ER stress inhibitor) and CHOP gene silencing. Additionally, diphenyleneiodonium (DPI, an oxidative stress inhibitor), probucol (a reactive oxygen species scavenger), and toll-like receptor 4 (TLR4) silencing reduced ox-HDL-induced macrophage apoptosis, oxidative stress, and CHOP upregulation. Moreover, HDL isolated from patients with metabolic syndrome induced macrophage apoptosis, oxidative stress, and CHOP upregulation, which were blocked by PBA and DPI. These data indicate that ox-HDL may activate ER stress-CHOP-induced apoptotic pathway in macrophages via enhanced oxidative stress and that this pathway may be mediated by TLR4.

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“…However, oxidized HDL causes the risk of atherosclerosis through the loss of their anti-atherogenic functions and increased cytotoxicity, reactive oxygen species (ROS) production, and lipid accumulation [22,23]. Furthermore, it has been reported that plasma oxHDL levels in patients with DM and CHD are higher than in healthy humans [24,25]. Therefore, inhibitors of LDL and HDL oxidation could be a good strategy to prevent heart diseases.…”

Section: Introductionmentioning

confidence: 99%

Anti-Atherosclerotic Activity of (3R)-5-Hydroxymellein from an Endophytic Fungus Neofusicoccum parvum JS-0968 Derived from Vitex rotundifolia through the Inhibition of Lipoproteins Oxidation and Foam Cell Formation

Kim

Shim

2020

Biomolecules

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An endophytic fungus, Neofusicoccum parvum JS-0968, was isolated from a plant, Vitex rotundifolia. The chemical investigation of its cultures led to the isolation of a secondary metabolite, (3R)-5-hydroxymellein. It has been reported to have antifungal, antibacterial, and antioxidant activity, but there have been no previous reports on the effects of (3R)-5-hydroxymellein on atherosclerosis. The oxidation of lipoproteins and foam cell formation have been known to be significant in the development of atherosclerosis. Therefore, we investigated the inhibitory effects of (3R)-5-hydroxymellein on atherosclerosis through low-density lipoprotein (LDL) and high-density lipoprotein (HDL) oxidation and macrophage foam cell formation. LDL and HDL oxidation were determined by measuring the production of conjugated dienes and malondialdehyde, the amount of hyperchromicity and carbonyl content, conformational changes, and anti-LDL oxidation. In addition, the inhibition of foam cell formation was measured by Oil red O staining. As a result, (3R)-5-hydroxymellein suppressed the oxidation of LDL and HDL through the inhibition of lipid peroxidation, the decrease of negative charges, the reduction of hyperchromicity and carbonyl contents, and the prevention of apolipoprotein A-I (ApoA-I) aggregation and apoB-100 fragmentation. Furthermore, (3R)-5-hydroxymellein significantly reduced foam cell formation induced by oxidized LDL (oxLDL). Taken together, our data show that (3R)-5-hydroxymellein could be a potential preventive agent for atherosclerosis via obvious anti-LDL and HDL oxidation and the inhibition of foam cell formation.

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Oxidized high-density lipoprotein is associated with increased plasma glucose in non-diabetic dyslipidemic subjects

Cited by 17 publications

References 46 publications

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

High-Density Lipoprotein: From Biological Functions to Clinical Perspectives

Oxidized high density lipoprotein induces macrophage apoptosis via toll-like receptor 4-dependent CHOP pathway

Anti-Atherosclerotic Activity of (3R)-5-Hydroxymellein from an Endophytic Fungus Neofusicoccum parvum JS-0968 Derived from Vitex rotundifolia through the Inhibition of Lipoproteins Oxidation and Foam Cell Formation

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