scholarly journals Structure and Dynamics of Oxidized Lipoproteins In Vivo: Roles of High-Density Lipoprotein

Biomedicines ◽  
2021 ◽  
Vol 9 (6) ◽  
pp. 655
Author(s):  
Hiroyuki Itabe ◽  
Naoko Sawada ◽  
Tomohiko Makiyama ◽  
Takashi Obama
Keyword(s):  
Cardiovascular Diseases ◽  
High Density Lipoprotein ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
High Density ◽  
Oxidative Modification ◽  
Foam Cell Formation ◽  
Oxidized Lipoproteins

Oxidative modification of lipoproteins is implicated in the occurrence and development of atherosclerotic lesions. Earlier studies have elucidated on the mechanisms of foam cell formation and lipid accumulation in these lesions, which is mediated by scavenger receptor-mediated endocytosis of oxidized low-density lipoprotein (oxLDL). Mounting clinical evidence has supported the involvement of oxLDL in cardiovascular diseases. High-density lipoprotein (HDL) is known as anti-atherogenic; however, recent studies have shown circulating oxidized HDL (oxHDL) is related to cardiovascular diseases. A modified structure of oxLDL, which was increased in the plasma of patients with acute myocardial infarction, was characterized. It had two unique features: (1) a fraction of oxLDL accompanied oxHDL, and (2) apoA1 was heavily modified, while modification of apoB, and the accumulation of oxidized phosphatidylcholine (oxPC) and lysophosphatidylcholine (lysoPC) was less pronounced. When LDL and HDL were present at the same time, oxidized lipoproteins actively interacted with each other, and oxPC and lysoPC were transferred to another lipoprotein particle and enzymatically metabolized rapidly. This brief review provides a novel view on the dynamics of oxLDL and oxHDL in circulation.

scholarly journals High-density lipoprotein or cyclodextrin extraction of cholesterol from aggregated LDL reduces foam cell formation

2019 ◽  
Vol 132 (23) ◽  
pp. jcs237271 ◽  
Author(s):  
Rajesh K. Singh ◽  
Frederik W. Lund ◽  
Abigail S. Haka ◽  
Frederick R. Maxfield
Keyword(s):  
High Density Lipoprotein ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
High Density ◽  
Foam Cell Formation

scholarly journals Neutrophils as a Novel Target of Modified Low-Density Lipoproteins and an Accelerator of Cardiovascular Diseases

2020 ◽  
Vol 21 (21) ◽  
pp. 8312
Author(s):  
Takashi Obama ◽  
Hiroyuki Itabe
Keyword(s):  
Cardiovascular Diseases ◽  
Inflammatory Responses ◽  
Foam Cell ◽  
Vascular Endothelial Cells ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Oxidative Modification ◽  
Foam Cell Formation ◽  
Low Density

Neutrophil extracellular traps (NETs) significantly contribute to various pathophysiological conditions, including cardiovascular diseases. NET formation in the vasculature exhibits inflammatory and thrombogenic activities on the endothelium. NETs are induced by various stimulants such as exogenous damage-associated molecular patterns (DAMPs). Oxidatively modified low-density lipoprotein (oxLDL) has been physiologically defined as a subpopulation of LDL that comprises various oxidative modifications in the protein components and oxidized lipids, which could act as DAMPs. oxLDL has been recognized as a crucial initiator and accelerator of atherosclerosis through foam cell formation by macrophages; however, recent studies have demonstrated that oxLDL stimulates neutrophils to induce NET formation and enhance NET-mediated inflammatory responses in vascular endothelial cells, thereby suggesting that oxLDL may be involved in cardiovascular diseases through neutrophil activation. As NETs comprise myeloperoxidase and proteases, they have the potential to mediate oxidative modification of LDL. This review summarizes recent updates on the analysis of NETs, their implications for cardiovascular diseases, and prospects for a possible link between NET formation and oxidative modification of lipoproteins.

scholarly journals Dysfunctional high-density lipoprotein from HIV+ individuals promotes monocyte-derived foam cell formation in vitro

AIDS ◽  
2017 ◽  
Vol 31 (17) ◽  
pp. 2331-2336 ◽  
Author(s):  
Thomas A. Angelovich ◽  
Anna C. Hearps ◽  
Michael N. Oda ◽  
Mark S. Borja ◽  
Diana Huynh ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Foam Cell ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
High Density ◽  
Foam Cell Formation

scholarly journals The Potential Role of Electronegative High-Density Lipoprotein H5 Subfraction in RA-Related Atherosclerosis

2021 ◽  
Vol 22 (21) ◽  
pp. 11419
Author(s):  
Ching-Kun Chang ◽  
Wei-Chung Cheng ◽  
Wen-Lung Ma ◽  
Po-Ku Chen ◽  
Chu-Huang Chen ◽  
...  
Keyword(s):  
High Density Lipoprotein ◽  
Foam Cell ◽  
Subclinical Atherosclerosis ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
High Density ◽  
Foam Cell Formation ◽  
Dependent Manner ◽  
Mrna And Protein Expression

Although the heterogeneity of high-density lipoprotein-cholesterol (HDL-c) composition is associated with atherosclerotic cardiovascular risk, the link between electronegative subfractions of HDL-c and atherosclerosis in rheumatoid arthritis (RA) remains unknown. We examined the association of the percentage of the most electronegative subfraction of HDL-c (H5%) and RA-related atherosclerosis. Using anion-exchange purification/fast-protein liquid chromatography, we demonstrated significantly higher H5% in patients (median, 7.2%) than HC (2.8%, p < 0.005). Multivariable regression analysis revealed H5% as a significant predictor for subclinical atherosclerosis. We subsequently explored atherogenic role of H5 using cell-based assay. The results showed significantly higher levels of IL-1β and IL-8 mRNA in H5-treated (mean ± SD, 4.45 ± 1.22 folds, 6.02 ± 1.43-folds, respectively) than H1-treated monocytes (0.89 ± 0.18-folds, 1.03 ± 0.26-folds, respectively, both p < 0.001). In macrophages, H5 upregulated the mRNA and protein expression of IL-1β and IL-8 in a dose-dependent manner, and their expression levels were significantly higher than H1-treated macrophages (all p < 0.001). H5 induced more foam cell formation compared with H1-treated macrophages (p < 0.005). In addition, H5 has significantly lower cholesterol efflux capacity than H1 (p < 0.005). The results of nanoLC-MS/MS approach reveal that the best discriminator between high-H5% and normal-H5% is Apo(a), the main constituent of Lp(a). Moreover, Lp(a) level is a significant predictor for high-H5%. These observations suggest that H5 is involved in RA-related atherosclerosis.

scholarly journals Modeling early stage atherosclerosis in a primary human vascular microphysiological system

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
Xu Zhang ◽  
Muath Bishawi ◽  
Ge Zhang ◽  
Varun Prasad ◽  
Ellen Salmon ◽  
...  
Keyword(s):  
Cell Activation ◽  
Foam Cell ◽  
Early Stage ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
No Production ◽  
Endothelial Cell Activation

Abstract Novel atherosclerosis models are needed to guide clinical therapy. Here, we report an in vitro model of early atherosclerosis by fabricating and perfusing multi-layer arteriole-scale human tissue-engineered blood vessels (TEBVs) by plastic compression. TEBVs maintain mechanical strength, vasoactivity, and nitric oxide (NO) production for at least 4 weeks. Perfusion of TEBVs at a physiological shear stress with enzyme-modified low-density-lipoprotein (eLDL) with or without TNFα promotes monocyte accumulation, reduces vasoactivity, alters NO production, which leads to endothelial cell activation, monocyte accumulation, foam cell formation and expression of pro-inflammatory cytokines. Removing eLDL leads to recovery of vasoactivity, but not loss of foam cells or recovery of permeability, while pretreatment with lovastatin or the P2Y11 inhibitor NF157 reduces monocyte accumulation and blocks foam cell formation. Perfusion with blood leads to increased monocyte adhesion. This atherosclerosis model can identify the role of drugs on specific vascular functions that cannot be assessed in vivo.

Abstract 570: Macrophage Catabolism of Aggregated Lipoproteins Using a Novel Extracellular Compartment Regulates Lipid Accumulation During Atherosclerosis

2017 ◽  
Vol 37 (suppl_1) ◽  
Author(s):  
Rajesh K Singh ◽  
Abigail S Haka ◽  
Valeria C Barbosa-Lorenzi ◽  
Arky Asmal ◽  
Frederik Lund ◽  
...  
Keyword(s):  
Lipid Accumulation ◽  
Actin Polymerization ◽  
Foam Cell ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Foam Cell Formation ◽  
Atherosclerotic Vascular Disease ◽  
Extracellular Compartment

Despite impressive advances in research, prevention, and treatment, atherosclerotic vascular disease remains the leading cause of death in the developed world. Mechanisms of cholesterol accumulation in the arteries have been studied intensively, but the in vivo contributions of different pathways leading to lipid accumulation and foam cell formation are not understood. In the arteries, low-density lipoprotein (LDL) is aggregated and bound to the extracellular matrix. When such aggregated LDL is presented to macrophages, they form a novel acidic, hydrolytic compartment that is topologically extracellular, to which lysosomal enzymes are secreted. Such compartments are observed in vivo in murine atherosclerotic plaque macrophages interacting with cholesterol rich deposits. Using state-of-the-art quantitative and high resolution microscopy techniques, characterization of compartment morphology reveals how macrophages use local actin polymerization to drive plasma membrane remodeling at the interface with aggregated LDL. This leads to sequestration of aggregated LDL into topologically convoluted structures that allow acidification, catabolism and internalization of LDL. We find that a TLR4/MyD88/Syk/PI3 kinase/Akt dependent signaling pathway in macrophages regulates the formation of such catabolic compartments. Consistent with this, deficiency of TLR4 in vivo can protect macrophages from lipid accumulation in murine atherosclerotic plaques. Herein, we provide compelling evidence for a novel form of catabolism that macrophages use to degrade aggregated LDL in vivo during atherosclerosis and this process leads to foam cell formation, cell death and promotes disease progression.

scholarly journals Low-Density Lipoprotein Modified by Myeloperoxidase in Inflammatory Pathways and Clinical Studies

2013 ◽  
Vol 2013 ◽  
pp. 1-18 ◽  
Author(s):  
Cédric Delporte ◽  
Pierre Van Antwerpen ◽  
Luc Vanhamme ◽  
Thierry Roumeguère ◽  
Karim Zouaoui Boudjeltia
Keyword(s):  
Endothelial Cells ◽  
Foam Cell ◽  
Thrombus Formation ◽  
Low Density Lipoprotein ◽  
Cell Formation ◽  
Density Lipoprotein ◽  
Ldl Oxidation ◽  
Foam Cell Formation ◽  
Low Density ◽  
Oxidized Lipoproteins

Oxidation of low-density lipoprotein (LDL) has a key role in atherogenesis. Among the different models of oxidation that have been studied, the one using myeloperoxidase (MPO) is thought to be more physiopathologically relevant. Apolipoprotein B-100 is the unique protein of LDL and is the major target of MPO. Furthermore, MPO rapidly adsorbs at the surface of LDL, promoting oxidation of amino acid residues and formation of oxidized lipoproteins that are commonly named Mox-LDL. The latter is not recognized by the LDL receptor and is accumulated by macrophages. In the context of atherogenesis, Mox-LDL accumulates in macrophages leading to foam cell formation. Furthermore, Mox-LDL seems to have specific effects and triggers inflammation. Indeed, those oxidized lipoproteins activate endothelial cells and monocytes/macrophages and induce proinflammatory molecules such as TNFαand IL-8. Mox-LDL may also inhibit fibrinolysis mediated via endothelial cells and consecutively increase the risk of thrombus formation. Finally, Mox-LDL has been involved in the physiopathology of several diseases linked to atherosclerosis such as kidney failure and consequent hemodialysis therapy, erectile dysfunction, and sleep restriction. All these issues show that the investigations of MPO-dependent LDL oxidation are of importance to better understand the inflammatory context of atherosclerosis.

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