Other forms of oxidized LDL: Emerging functions (Review)

Daher, Jalil

doi:10.3892/wasj.2020.45

Cited by 6 publications

(12 citation statements)

References 22 publications

(20 reference statements)

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“…It has been previously reported that MoxLDL triggers inflammatory pathways in both macrophages and endothelial cells [ 7 ] and that Mox-LDL treatment was found to induce IL-8 release in endothelial cells in a dose dependent manner [ 43 ]. IL-8 plays a crucial role in atherogenesis where it acts as a chemoattractant to inflammatory cells and also to smooth muscle cells where it is involved in their migration to the intima and the formation of the fibrous cap [ 28 , 44 ].…”

Section: Discussionmentioning

confidence: 99%

“…Many studies have reported that patients with MPO-deficiency have a reduced risk of cardiovascular disease [ 4 , 6 ]. Other studies have also shown a correlation between myeloperoxidase oxidized LDL (Mox-LDL) and different levels of endothelial cell dysfunction (ED) [ 7 ]. As far as atherosclerosis is concerned, ED and circulating endothelial cells are associated with plaque rupture, stroke, and myocardial infarction [ 8 ].…”

Section: Introductionmentioning

confidence: 99%

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Myeloperoxidase-Oxidized LDL Activates Human Aortic Endothelial Cells through the LOX-1 Scavenger Receptor

El-Hajjar

Hindieh

Andraos

et al. 2022

IJMS

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Cardiovascular disease as a result of atherosclerosis is a leading cause of death worldwide. Atherosclerosis is primarily caused by the dysfunction of vascular endothelial cells and the subendothelial accumulation of oxidized forms of low-density lipoprotein (LDL). Early observations have linked oxidized LDL effects in atherogenesis to the lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) scavenger receptor. It was shown that LOX-1 is upregulated by many inflammatory mediators and proatherogenic stimuli including cytokines, reactive oxygen species (ROS), hemodynamic blood flow, high blood sugar levels and, most importantly, modified forms of LDL. Oxidized LDL signaling pathways in atherosclerosis were first explored using LDL that is oxidized by copper (Cuox-LDL). In our study, we used a more physiologically relevant model of LDL oxidation and showed, for the first time, that myeloperoxidase oxidized LDL (Mox-LDL) may affect human aortic endothelial cell (HAEC) function through the LOX-1 scavenger receptor. We report that Mox-LDL increases the expression of its own LOX-1 receptor in HAECs, enhancing inflammation and simultaneously decreasing tubulogenesis in the cells. We hypothesize that Mox-LDL drives endothelial dysfunction (ED) through LOX-1 which provides an initial hint to the pathways that are initiated by Mox-LDL during ED and the progression of atherosclerosis.

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Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Myeloperoxidase-Oxidized LDL Activates Human Aortic Endothelial Cells through the LOX-1 Scavenger Receptor

El-Hajjar

Hindieh

Andraos

et al. 2022

IJMS

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“…This might be related to the fact that lipoprotein quality is crucial in mediating atherogenesis; in fact, LDL is post-translationally modified in several processes such as glycation, glycosylation, carbamylation, glycoxidation, acetylation, methylation, ethylation, and oxidation ( 10 , 36 ). Interestingly, one of the most significant LDL modifications is oxidation, which results in the generation of an inflammatory form known as highly oxLDL ( 7 ). The oxidation of LDL occurs along an extensive and continuous spectrum.…”

Section: Oxidized Ldl (Oxldl) and Atherosclerosismentioning

confidence: 99%

“…Immunohistochemical analysis reported the presence of MPO in atheroma plaques of human patients and several studies have also shown its co-localization with HOCl-modified low-density lipoproteins (LDLs) in human atherosclerotic lesions where it can be found in both vascular cells and in extracellular spaces ( 4 , 5 ). Thus, MPO and its downstream products, mainly HOCl, are known to be implicated in the pathophysiology of atherosclerotic diseases ( 6 , 7 ). Despite the fact that several processes are reported to be responsible for the oxidation of LDL both in in vitro and in vivo settings, LDL that is oxidized by MPO remains the most physiologically relevant type of oxidized LDL (oxLDL) with considerable evidence confirming this theory.…”

Section: Introductionmentioning

confidence: 99%

“…Despite the fact that several processes are reported to be responsible for the oxidation of LDL both in in vitro and in vivo settings, LDL that is oxidized by MPO remains the most physiologically relevant type of oxidized LDL (oxLDL) with considerable evidence confirming this theory. LDL that is modified by the MPO system affects multiple cells that are found in the atheroma plaques; this includes endothelial cells (ECs), macrophages, and smooth muscle cells ( 7 ). In this review, we describe the involvement of MPO in health and disease with an emphasis on the role of MPO oxLDL (Mox-LDL) in macrophage and endothelial dysfunction (ED) in the context of atherosclerosis.…”

Section: Introductionmentioning

confidence: 99%

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Role of myeloperoxidase in inflammation and atherosclerosis (Review)

Frangie

Daher

2022

Biomed Rep

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Myeloperoxidase (MPO) belongs to the heme peroxidase family, which includes a set of enzymes with potent oxidoreductase activity. MPO is considered an important part of the innate immune system's microbicidal arm and is secreted by neutrophils and macrophages. Interestingly, this enzyme has been implicated in the pathogenesis of several diseases including atherosclerosis. MPO is ubiquitous in atherosclerotic lesions and contributes to the initiation and progression of the disease primarily by oxidizing low-density lipoprotein (LDL) particles. MPO is the only human enzyme with the ability to produce hypochlorous acid (HOCl) at physiological chloride concentrations and HOCl-LDL epitopes were shown to be present inside atheromatous lesions making it a physiologically relevant model for the oxidation of LDL. It has been shown that MPO modified LDL is not able to bind to the native LDL receptor and is recognized instead by scavenger receptors on both endothelial cells and macrophages, which can lead to endothelial dysfunction and foam cell formation, respectively; both of which are instrumental in the progression of the disease. Meanwhile, several studies have proposed MPO as a biomarker for cardiovascular diseases where high levels of this enzyme were linked to an increased risk of developing coronary artery disease. Overall, there is sufficient evidence supporting the value of MPO as a crucial player in health and disease. Thus, future research should be directed towards investigating the still unknown processes associated with this enzyme. This may assist in better understanding the pathophysiological role of MPO, as well in the development of therapeutic strategies for protecting against the deleterious effects of MPO in numerous pathologies such as atherosclerosis.

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A novel insight into the nature of modified low-density lipoproteins and their role in atherosclerosis

2023

Vessel Plus

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Atherosclerosis plays a significant role in the development of cardiovascular diseases, the leading cause of death worldwide. Modification of low-density lipoproteins (LDLs) is a critical event in atherogenesis. Native LDL undergoes several modifications that can lead to the formation of atherogenic modified LDLs. LDL modifications change their physicochemical and biological properties. Possible modifications include changes in the lipoprotein particle's structure, size, charge, and composition. Uptake and utilization of modified LDLs are impaired in cells. Macrophages take up modified LDLs that promote forming of foam cells, one of the critical cellular components of atherosclerotic lesions. Nevertheless, the direct role of each atherogenic LDL modification in atherogenesis remains uncertain. This review highlights LDL's most critical atherogenic modifications, including oxidized, enzymemodified, non-oxidative, desialylated, glycated and carbamylated LDLs. Studying the role of each type of LDL modification will clarify the unknown elements of atherosclerosis progression and facilitate the development of effective methods for its diagnosis, treatment, and prevention.

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Other forms of oxidized LDL: Emerging functions (Review)

Cited by 6 publications

References 22 publications

Myeloperoxidase-Oxidized LDL Activates Human Aortic Endothelial Cells through the LOX-1 Scavenger Receptor

Myeloperoxidase-Oxidized LDL Activates Human Aortic Endothelial Cells through the LOX-1 Scavenger Receptor

Role of myeloperoxidase in inflammation and atherosclerosis (Review)

A novel insight into the nature of modified low-density lipoproteins and their role in atherosclerosis

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