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

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.

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Oxidative modification of beta-very low density lipoprotein. Potential role in monocyte recruitment and foam cell formation.

Arteriosclerosis An Official Journal of the American Heart Association Inc ◽

10.1161/01.atv.9.3.398 ◽

1989 ◽

Vol 9 (3) ◽

pp. 398-404 ◽

Cited By ~ 109

Author(s):

S Parthasarathy ◽

M T Quinn ◽

D C Schwenke ◽

T E Carew ◽

D Steinberg

Keyword(s):

Potential Role ◽

Foam Cell ◽

Low Density Lipoprotein ◽

Cell Formation ◽

Density Lipoprotein ◽

Oxidative Modification ◽

Foam Cell Formation ◽

Very Low Density Lipoprotein ◽

Low Density ◽

Monocyte Recruitment

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Foam Cell Formation through Oxidative Modification of Glycosylated Low Density Lipoprotein

The Journal of Japan Atherosclerosis Society ◽

10.5551/jat1973.24.3_117 ◽

1996 ◽

Vol 24 (3) ◽

pp. 117-125

Author(s):

Mitsunobu KAWAMURA ◽

Shigeru MIYAZAKI ◽

Tamio TERAMOTO ◽

Makoto KINOSHITA

Keyword(s):

Foam Cell ◽

Low Density Lipoprotein ◽

Cell Formation ◽

Density Lipoprotein ◽

Oxidative Modification ◽

Foam Cell Formation ◽

Low Density

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Protective Effect of Lusianthridin on Hemin-Induced Low-Density Lipoprotein Oxidation

Pharmaceuticals ◽

10.3390/ph14060567 ◽

2021 ◽

Vol 14 (6) ◽

pp. 567

Author(s):

Su Wutyi Thant ◽

Noppawan Phumala Morales ◽

Visarut Buranasudja ◽

Boonchoo Sritularak ◽

Rataya Luechapudiporn

Keyword(s):

Foam Cell ◽

Low Density Lipoprotein ◽

Cell Formation ◽

Density Lipoprotein ◽

Foam Cell Formation ◽

Raw 264.7 ◽

Low Density ◽

Lipoprotein Oxidation ◽

Raw 264.7 Macrophage Cells ◽

Low Density Lipoprotein Oxidation

Oxidation of low-density lipoprotein (LDL) plays a crucial role in the pathogenesis of atherosclerosis. Hemin (iron (III)-protoporphyrin IX) is a degradation product of hemoglobin that can be found in thalassemia patients. Hemin is a strong oxidant that can cause LDL oxidation and contributes to atherosclerosis in thalassemia patients. Lusianthridin from Dendrobium venustrum is a phenolic compound that possesses antioxidant activity. Hence, lusianthridin could be a promising compound to be used against hemin-induced oxidative stress. The major goal of this study is to evaluate the protective effect of lusianthridin on hemin-induced low-density lipoprotein oxidation (he-oxLDL). Here, various concentrations of lusianthridin (0.25, 0.5, 1, and 2 µM) were preincubated with LDL for 30 min, then 5 µM of hemin was added to initiate the oxidation, and oxidative parameters were measured at various times of incubation (0, 1, 3, 6, 12, 24 h). Lipid peroxidation of LDL was measured by thiobarbituric reactive substance (TBARs) assay and relative electrophoretic mobility (REM). The lipid composition of LDL was analyzed by using reverse-phase HPLC. Foam cell formation with he-oxLDL in RAW 264.7 macrophage cells was detected by Oil Red O staining. The results indicated that lusianthridin could inhibit TBARs formation, decrease REM, decrease oxidized lipid products, as well as preserve the level of cholesteryl arachidonate and cholesteryl linoleate. Moreover, He-oxLDL incubated with lusianthridin for 24 h can reduce the foam cell formation in RAW 264.7 macrophage cells. Taken together, lusianthridin could be a potential agent to be used to prevent atherosclerosis in thalassemia patients.

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

Biomedicines ◽

10.3390/biomedicines9060655 ◽

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.

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