Dual effect of oxidized LDL on cell cycle in human endothelial cells through oxidative stress

Galle, Jan; Heinloth, Alexandra N.; Wanner, Christoph; Heermeier, Kathrin

doi:10.1046/j.1523-1755.2001.07836.x

Cited by 41 publications

(39 citation statements)

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“…Previous studies demonstrated that oxLDL evoked an oxidative burst in endothelial cells (39 -41) and/or monocyte/macrophage cell lines (33). Antisense oligonucleotides directed against p22 phox , a subunit of the membrane-bound NAD(P)H oxidase system, attenuated oxLDL-evoked ROS formation in endothelial cells, suggesting a role for membrane-bound NAD(P)H oxidase as a major source of ROS (34,42). We corroborated these findings by eliminating ROS generation in macrophages with the use of DPI, an inhibitor for O 2 Ϫ -producing NAD(P)H-like oxidase systems.…”

Section: Discussionmentioning

confidence: 95%

Dualism of Oxidized Lipoproteins in Provoking and Attenuating the Oxidative Burst in Macrophages: Role of Peroxisome Proliferator-Activated Receptor-γ

Fischer

Knethen

Brüne

2002

The Journal of Immunology

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Activation and deactivation of macrophages are of considerable importance during the development of various disease states, atherosclerosis among others. Macrophage activation is achieved by oxidized lipoproteins (oxLDL) and is determined by oxygen radical (ROS) formation. The oxidative burst was measured by flow cytometry and quantitated by oxidation of the redox-sensitive dye dichlorodihydrofluorescein diacetate. Short-time stimulation dose-dependently elicited ROS formation. Diphenylene iodonium prevented ROS formation, thus pointing to the involvement of a NAD(P)H oxidase in producing reduced oxygen species. In contrast, preincubation of macrophages with oxLDL for 16 h showed an attenuated oxidative burst upon a second contact with oxLDL. Taking into account that oxLDL is an established peroxisome proliferator-activated receptor-γ (PPARγ) agonist and considering the anti-inflammatory properties of PPARγ, we went on and showed that a PPARγ agonist such as ciglitazone attenuated ROS formation. Along that line, major lipid peroxidation products of oxLDL, such as 9- and 13-hydroxyoctadecadienoic acid, shared that performance. Supporting evidence that PPARγ activation accounted for reduced ROS generation came from studies in which proliferator-activated receptor response element decoy oligonucleotides, but not a mutated oligonucleotide, supplied in front of oxLDL delivery regained a complete oxidative burst upon cell activation. We conclude that oxLDL not only elicits an oxidative burst upon first contact, but also promotes desensitization of macrophages via activation of PPARγ. Desensitization of macrophages may have important consequences for the behavior of macrophages/foam cells in atherosclerotic lesions.

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Section: Discussionmentioning

confidence: 95%

Dualism of Oxidized Lipoproteins in Provoking and Attenuating the Oxidative Burst in Macrophages: Role of Peroxisome Proliferator-Activated Receptor-γ

Fischer

Knethen

Brüne

2002

The Journal of Immunology

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“…Ox-LDL has dual effects on cultured cells depending on its concentration and the exposure time. Ox-LDL induces proliferation at lower concentration and shorter exposure time, whereas at higher concentration and longer exposure time it induces apoptosis and even necrosis (Galle et al 2001;Seibold et al 2004). Galle et al (2001) also showed that both the proliferative and apoptotic effects of ox-LDL are mediated by superoxide anion formation.…”

Section: X-p Chen Et Almentioning

confidence: 99%

“…Ox-LDL induces proliferation at lower concentration and shorter exposure time, whereas at higher concentration and longer exposure time it induces apoptosis and even necrosis (Galle et al 2001;Seibold et al 2004). Galle et al (2001) also showed that both the proliferative and apoptotic effects of ox-LDL are mediated by superoxide anion formation. Akagi et al (2006) reported that the synergistic effects of cyclic tensile stretch load and ox-LDL on cell viability and proteoglycan synthesis may be mediated through enhanced expression of LOX-1 in cultured bovine chondrocytes.…”

Section: X-p Chen Et Almentioning

confidence: 99%

Lectin‐like Oxidized Low‐density Lipoprotein Receptor‐1, a New Promising Target for the Therapy of Atherosclerosis?

Chen

Zhang

2007

Cardiovascular Drug Reviews

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Endothelial activation and dysfunction induced by oxidized modified low-density lipoprotein (ox-LDL) is one of the key steps in the initiation of atherosclerosis. Recent studies have shown that a new lectin-like oxidized low-density lipoprotein receptor-1 (LOX-1) mediates the recognition and internalization of ox-LDL. LOX-1 is the main receptor for ox-LDL and may play an important role in the pathogenesis of hypertension, diabetes, and, especially, of atherosclerosis. The potential role of LOX-1 in the pathogenesis of atherosclerosis includes: endocytosis of ox-LDL, expression co-location with atherosclerosis enhanced by atherosclerosis-related risk factors, elevated LOX-1 protein in cardiovascular disease, effects related to atherosclerosis and eliminated by antiatherosclerotic drugs. Identification and regulation of LOX-1 and understanding its signal transduction pathways might improve our insight toward the pathogenesis of atherosclerosis and provide a selective treatment approach. LOX-1 might be a potential and promising target for the development of novel antiatherosclerotic drugs. However, due to limited knowledge about LOX-1, there are still many questions to be answered.

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“…Oxidized LDL (oxLDL), the most intensively studied modified LDL, has been shown to induce endothelial cell death in vitro (31). The cytotoxic effect of oxLDL is often associated with cell proliferation (16). The combination of cell proliferation and cell death results in the high turnover of vascular endothelial cells, which is an important characteristic of atherosclerosis (25).…”

mentioning

confidence: 99%

Modified LDLs induce proliferation-mediated death of human vascular endothelial cells through MAPK pathway

Apostolov¹,

Basnakian²,

Yin³

et al. 2007

American Journal of Physiology-Heart and Circulatory Physiology

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Apostolov EO, Basnakian AG, Yin X, Ok E, Shah SV. Modified LDLs induce proliferation-mediated death of human vascular endothelial cells through MAPK pathway. Am J Physiol Heart Circ Physiol 292: H1836 -H1846, 2007. First published December 22, 2006; doi:10.1152/ajpheart.01079.2006.-The ability of modified low-density lipoptoteins (LDLs) to induce both proliferation and death of endothelial cells is considered to be a mechanism of early atherosclerosis development. We previously showed that carbamylated LDL (cLDL) induces human coronary artery endothelial cell (HCAEC) death in vitro. This effect is similar to the atherogenic action of oxidized LDL (oxLDL) that induces the proliferation and death of endothelial cells. The present study was designed to analyze a potential proliferative effect of cLDL and whether proliferation caused by modified LDLs is related to cell death. Cultured HCAECs were exposed to different concentrations of modified LDL or native LDL for varying periods of time. Cell proliferation measured by bromodeoxyuridine incorporation and S-phase analysis was dosedependently increased in the presence of cLDL (6.25-200 g/ml). The proliferation induced by cLDL or oxLDL was associated with cell death and increased phosphorylation of extracellular signal-regulated kinase (ERK) and c-Jun NH 2-terminal kinase (JNK). Inhibition of cLDL-or oxLDL-induced proliferation by aphidicolin (1 g/ml) was protective against both short-term cell death measured by lactate dehydrogenase release into the medium and long-term cell viability visualized by cell multiplication. Inhibition of ERK phosphorylation led to a significant decrease of DNA synthesis and cell rescue from injury by modified LDLs, while inhibition of JNK phosphorylation had an only partial rescue effect without involvement in cell proliferation. These data are the first evidence that endothelial cell death induced by cLDL or oxLDL is mediated by cell proliferation through the mitogen-activated protein kinase pathway. carbamylation; carbamylated low-density lipoprotein; oxidized lowdensity lipoprotein; mitogen-activated protein kinase; atherosclerosis CARBAMYLATION is a spontaneous, nonenzymatic reaction of protein modification by cyanate derived from urea, which is normally present in human plasma and is elevated in uremic patients (27). Chronic kidney disease in humans is associated with a several times increased risk of developing cardiovascular diseases because of accelerated atherosclerosis (12,32,47). The mechanism of uremia-induced atherosclerosis is not quite understood. We previously showed (2, 36, 37) that carbamylated low-density lipoprotein (cLDL) induces injury or dysfunction of endothelial cells and is present in human plasma in high quantities. Our recent observation (38) that cLDL induces cell death of human coronary artery endothelial cells (HCAECs) in vitro provided support for this hypothesis.It is commonly accepted that modified LDLs are important for early atherosclerosis initiation and progression (39, 43). Endothelial dysfunction i...

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Dual effect of oxidized LDL on cell cycle in human endothelial cells through oxidative stress

Cited by 41 publications

References 0 publications

Dualism of Oxidized Lipoproteins in Provoking and Attenuating the Oxidative Burst in Macrophages: Role of Peroxisome Proliferator-Activated Receptor-γ

Dualism of Oxidized Lipoproteins in Provoking and Attenuating the Oxidative Burst in Macrophages: Role of Peroxisome Proliferator-Activated Receptor-γ

Lectin‐like Oxidized Low‐density Lipoprotein Receptor‐1, a New Promising Target for the Therapy of Atherosclerosis?

Modified LDLs induce proliferation-mediated death of human vascular endothelial cells through MAPK pathway

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