HDL derived from the different phases of conjugated diene formation reduces membrane fluidity and contributes to a decrease in free cholesterol efflux from human THP-1 macrophages

Girona, Josefa; Laville, A.; Solà, Rosa; Motta, Claude; Masana, Luís

doi:10.1016/s1388-1981(03)00108-2

Cited by 25 publications

(12 citation statements)

References 30 publications

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“…Contrary to the ABCA1-mediated cholesterol efflux, the other implicated mechanisms, ABCG1 and ABCG4, the spontaneous transfer, and the SR-BI pathways, all involve cholesterol transfer to phospholipid-containing species, principally HDL 2 (42). Thus, one might expect that alteration or change in the HDL phospholipid composition or structure would affect RCT (42)(43)(44). Analysis of the HDL, HDL 2 , and HDL 3 phospholipid composition as a function of donor age showed a significant decrease in the PC/ SPM ratio in the elderly.…”

Section: Discussionmentioning

confidence: 99%

Age-related impairment of HDL-mediated cholesterol efflux

Berrougui

Isabelle

Cloutier

et al. 2007

Journal of Lipid Research

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Our aim in this study was to investigate the effect of aging on the capacity of HDLs to promote reverse cholesterol transport. HDLs were isolated from plasma of young (Y-HDL) and elderly (E-HDL) subjects. HDL-mediated cholesterol efflux was studied using THP-1 and J774 macrophages. Our results show that E-HDLs present a lower capacity to promote cholesterol efflux than Y-HDLs (41.7 6 1.4% vs. 49.0 6 2.2%, respectively; P 5 0.013). Reduction in the HDL-mediated cholesterol efflux capacity with aging was more significant with HDL 3 than HDL 2 (Y-HDL 3 , 57.3 6 1% vs. E-HDL 3 , 50.9 6 2%; P 5 0.012). Moreover, our results show that ABCA1-mediated cholesterol efflux is the more affected pathway in terms of cholesterol-removing capacity. Interestingly, the composition and structure of HDL revealed a reduction in the phosphatidylcholine-sphingomyelin ratio (E-HDL, 32.7 6 2.7 vs. Y-HDL, 40.0 6 1.9; P 5 0.029) and in the phospholipidic layer membrane fluidity in E-HDL compared with Y-HDL as well as an alteration in the apolipoprotein A-I structure and charge. In conclusion, our results shown that E-HDLs present a reduced capacity to promote cholesterol efflux, principally through the ABCA1 pathway, and this may explain the increase of the incidence of cardiovascular diseases observed during aging.-Berrougui, H., M. Isabelle, M. Cloutier, G. Grenier, and A. Khalil. Age-related impairment of HDL-mediated cholesterol efflux. J. Lipid Res. 2007. 48: 328-336.

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Section: Discussionmentioning

confidence: 99%

Age-related impairment of HDL-mediated cholesterol efflux

Berrougui

Isabelle

Cloutier

et al. 2007

Journal of Lipid Research

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“…The isolated LDL and HDL were dialyzed extensively against endotoxin-free PBS (pH = 7.4) containing 0.1 mmol/L EDTA at 4°C and sterilized with a 0.22 µm filter. Ox-LDL and ox-HDL were prepared by incubating native LDL (n-LDL; 1 mg/ml) and native HDL (n-HDL; 1 mg/ml) under sterile conditions with 10 µmol/L CuSO 4 in EDTA-free PBS at 37°C for 24 h, as has been described previously (18,21). Oxidative modification was prevented by addition of EDTA, and then the oxidized lipoproteins were stored at 4°C and used within 2 weeks.…”

Section: Lipoprotein Preparation and Oxidationmentioning

confidence: 99%

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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“…21 The reasons for the reduced ability to remove PON1 from the cell are not clear, although it does mirror the reduced capacity to efflux cholesterol to HDLox. 3,27 Modifications to the peptide components of HDL do not appear to be a major determinant as suggested by the studies with HDL-OCl.…”

Section: Discussionmentioning

confidence: 92%

“…This could exacerbate the effects of oxidation on other HDL functions. The capacity of HDL to promote cholesterol efflux is diminished 3,27 (a facilitating role for PON1 in cholesterol efflux has recently been proposed 28 ). In this context, oxidation of HDL influences ABCA1 mediated cholesterol transport.…”

Section: Discussionmentioning

confidence: 99%

HDL Oxidation Compromises its Influence on Paraoxonase-1 Secretion and its Capacity to Modulate Enzyme Activity

Deakin

Moren

James

2007

ATVB

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Objective-The purpose of this study was to analyze the consequences of HDL oxidation for paraoxonase-1 metabolism and function. Methods and Results-HDL was oxidized with AAPH, copper ions, and hypochlorite. Secretion studies were performed using human paraoxonase-1-transfected cells lines and primary rat hepatocytes. Stability studies were performed with recombinant paraoxonase. Conditioned medium had significantly reduced paraoxonase-1 when Cu or AAPH-oxidized HDL was the acceptor complex (PϽ0.01); reduction was dose-dependent on the degree of oxidation. Oxidized HDL had a reduced capacity to stabilize/improve activity of secreted paraoxonase-1. Reduced secretion could not be attributed to enzyme inactivation by lipoperoxides, reduced binding affinity of HDL, or oxidation of the lipid component alone. Hypochlorite oxidation of HDL did not modify HDL-mediated paraoxonase-1 release, but activity of HDL-associated paraoxonase-1 was particularly sensitive to such treatment. Conclusions-AAPH and copper, but not hypochlorite, oxidation of HDL compromises its ability to promote release of paraoxonase-1 and stabilize enzyme activity. HDL-associated paraoxonase-1 is highly sensitive to hypochlorite. Reducing paraoxonase-1 renders HDL susceptible to oxidation, which may compromise HDL function. It provides a novel example at the HDL level of the detrimental effects of oxidative stress, and underlines the need for further evaluation of the consequences of HDL oxidation.

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HDL derived from the different phases of conjugated diene formation reduces membrane fluidity and contributes to a decrease in free cholesterol efflux from human THP-1 macrophages

Cited by 25 publications

References 30 publications

Age-related impairment of HDL-mediated cholesterol efflux

Age-related impairment of HDL-mediated cholesterol efflux

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

HDL Oxidation Compromises its Influence on Paraoxonase-1 Secretion and its Capacity to Modulate Enzyme Activity

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