Oxidized Low-Density Lipoprotein Stimulates p53-Dependent Activation of Proapoptotic Bax Leading to Apoptosis of Differentiated Endothelial Progenitor Cells

Cheng, Jizhong; Cui, Ruwen; Chen, Chu‐Huang; Du, Jie

doi:10.1210/en.2006-1709

Cited by 73 publications

(60 citation statements)

References 47 publications

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“…Some data have indicated the possibility of p53-dependent apoptosis induced by oxidatively modified LDL due to the release of reactive oxygen species (ROS) by disrupted mitochondria [6]. Thus, the mechanism underlying the triggering of apoptosis in cells by HOCl-modified phosphatidylcholines may be similar to that found for oxLDL.…”

Section: Discussionmentioning

confidence: 95%

“…Apoptotic endothelial cells have been demonstrated to release IL-1 and adhesion molecules, as well as to have reduced production of NO and prostacyclins, leading to platelet and neutrophil activation [1]. A number of reports have suggested that oxidatively-modified low density lipoproteins (ox-LDL) are pro-apoptotic factors and can be considered as one of the many risk factors in atherosclerosis [5,6]. In particular, modifications of the protein and lipids of the LDL fraction accelerate its uptake by macrophages, resulting in conversion of these cells into foam cells [7,8].…”

Section: Introductionmentioning

confidence: 99%

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HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells

Robaszkiewicz

Bartosz

Pitt

et al. 2014

Archives of Biochemistry and Biophysics

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Electrophilic attack of hypochlorous acid on unsaturated bonds of fatty acyl chains is known to result mostly in chlorinated products that show cytotoxicity to some cell lines and were found in biological systems exposed to HOCl. This study aimed to investigate more deeply the products and the mechanism underlying cytotoxicity of phospholipid-HOCl oxidation products, synthesized by the reaction of HOCl with 1-stearoyl-2-oleoyl-, 1-stearoyl-2-linoleoyl-, and 1-stearoyl-2-arachidonyl-phosphatidylcholine. Phospholipid chlorohydrins were found to be the most abundant among obtained products. HOCl-modified lipids were cytotoxic towards HUVEC-ST (endothelial cells), leading to a decrease of mitochondrial potential and an increase in the number of apoptotic cells. These effects were accompanied by an increase of the level of active caspase-3 and caspase-7, while the caspase-3/-7 inhibitor Ac-DEVD-CHO dramatically decreased the number of apoptotic cells. Phospholipid-HOCl oxidation products were shown to affect cell proliferation by a concentration-dependent cell cycle arrest in the G 0 /G 1 phase and activating redox sensitive p38 kinase. The redox imbalance observed in HUVEC-ST cells exposed to modified phosphatidylcholines was accompanied by an increase in ROS level, and a decrease in glutathione content and antioxidant capacity of cell extracts.

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Section: Discussionmentioning

confidence: 95%

Section: Introductionmentioning

confidence: 99%

HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells

Robaszkiewicz

Bartosz

Pitt

et al. 2014

Archives of Biochemistry and Biophysics

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“…34,35 Not recognized widely, low-concentration oxLDL may paradoxically protect endothelial cells against apoptosis provoked by high-concentration oxLDL. 36,37 We hypothesized that very low concentrations of oxLDL which are present during physiological state may have a nonpathologic role in cell biology. As endothelial cells grow and proliferate, they tend to from tubules.…”

Section: Discussionmentioning

confidence: 99%

Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

Dandapat

Sun

et al. 2007

ATVB

140

116

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Objective-Vascular endothelial growth factor (VEGF), a key angiogenic growth factor, stimulates angiogenesis. Low levels of reactive oxygen species (ROS) function as signaling molecules for angiogenesis. We postulated that low concentrations of oxLDL might induce low levels of ROS and initiate angiogenesis. Methods and Results-An in vitro model of tube formation from human coronary artery endothelial cells (HCAECs) was used.oxLDL (0.1, 1, 2, 5 g/mL) induced VEGF expression and enhanced tube formation. oxLDL-mediated VEGF expression and tube formation were suppressed by a specific blocking anti-LOX-1 antibody. Anti-LOX-1 antibody also reduced oxLDL-induced increase in the expression of NADPH oxidase (gp91 phox and p47 phox subunits) and subsequent intracellular ROS generation, phosphorylation of p38 as well as p44/42MAPK, and NF-B p65 expression. gp91 phox siRNA had a similar effect. The expression of VEGF and NF-B p65 induced by oxLDL was also inhibited by the specific extracellular signal-regulated kinase (ERK) 1/2 inhibitor U0126 and the p38 MAPK inhibitor SB203580. Importantly, the NADPH oxidase inhibitor apocynin, gp91 phox siRNA, U0126, and SB203580 all reduced tube formation in response to oxLDL. Conclusions-These

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“…Theoretically, the key players in CHD, i.e., blood monocytes, lymphocytes, endothelial cells, vascular fibroblasts, and smooth muscle cells, while engaged in the injury and repair struggle eventually giving rise to fatal plaque formation and rupture (41), might acquire fatal dysfunctions caused by diabetes-induced DNA damage. There is a wealth of detailed data on diabetes-related malfunctioning of these cells and platelets and on oxidative stress on endothelial cells in atherosclerosis (42). In addition, chromosomal alterations have been found in atherosclerotic plaques (43).…”

Section: Discussionmentioning

confidence: 99%

Lymphocytes of Type 2 Diabetic Women Carry a High Load of Stable Chromosomal Aberrations

Boehm

Möller²,

Högel³

et al. 2008

Diabetes

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OBJECTIVE-Diabetes is associated with an increased risk of death in women. Oxidative stress due to chronic hyperglycemia leads to the generation of reactive oxygen species and loss of chromosomal integrity. To clarify whether diabetes is a premature aging syndrome, we determined telomere erosion dynamics and occurrence of structural chromosomal aberrations in women of the Ludwigshafen Risk and Cardiovascular Health (LURIC) Study.RESEARCH DESIGN AND METHODS-Telomere lengths and karyotypes were examined in peripheral blood mononuclear cells. Regarding these parameters, surviving and deceased type 2 diabetic women of the LURIC study were compared with nondiabetic LURIC women with or without coronary heart disease and with healthy female control subjects.RESULTS-Significantly enhanced telomere attrition was seen in all LURIC subjects compared with healthy control subjects. Although the average telomere-length loss is equivalent to well Ͼ10 years of healthy aging, telomere erosion was not associated with outcome within the LURIC cohort. However, strikingly high numbers of stable chromosomal aberrations were found in type 2 diabetic women but not in LURIC disease control subjects or in healthy individuals. Furthermore, within the younger agegroups, deceased type 2 diabetes patients had significantly more marker chromosomes than the surviving type 2 diabetic patients.CONCLUSIONS-All women at high risk for cardiovascular death have accelerated telomere erosion, not caused by type 2 diabetes per se but likely linked to other risk factors, including dyslipidemia. By contrast, the occurrence of marker chromosomes is associated with type 2 diabetes and is a novel risk factor for type 2 diabetes-related early death. Diabetes 57:2950-2957, 2008 T ype 2 diabetes is characterized by increased morbidity and all-cause mortality (1,2). The combination of excess caloric intake and reduced physical activity leading to obesity, dyslipidemia, and hypertension increases the risk for diabetes and coronary heart disease (CHD). Recent data show that among diabetic men, the mortality rate has decreased significantly, whereas in diabetic women, no such trend was found (3). The all-cause mortality rate difference between diabetic and nondiabetic women is considerable. Therefore, the combination of diabetes with multiple risk factors identifies women at particularly high risk (2,4).The relative risk for morbidity and mortality in women with diabetes is increased compared with nondiabetic control subjects (2,5). Diabetes may therefore be regarded as a premature aging syndrome in which the overall metabolic shift leads to genotoxic stress that results in loss of chromosomal integrity (rev. in 6). Oxidative stress plays a crucial role in the pathogenesis of type 2 diabetes and in diabetes-associated complications. The generation of reactive oxygen species (ROS) is a common downstream mechanism whereby multiple by-products of glucose and (pro)inflammatory molecules exert adverse effects (7-11). DNA damage and telomere attrition can serve as marke...

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Oxidized Low-Density Lipoprotein Stimulates p53-Dependent Activation of Proapoptotic Bax Leading to Apoptosis of Differentiated Endothelial Progenitor Cells

Cited by 73 publications

References 47 publications

HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells

HOCl-modified phosphatidylcholines induce apoptosis and redox imbalance in HUVEC-ST cells

Small Concentrations of oxLDL Induce Capillary Tube Formation From Endothelial Cells via LOX-1–Dependent Redox-Sensitive Pathway

Lymphocytes of Type 2 Diabetic Women Carry a High Load of Stable Chromosomal Aberrations

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