Oxidized Lipoproteins and Endothelium

Pirillo, Angela; Zhu, Weimin; Norata, Giuseppe Danilo; Zanelli, Tiziano; Barberi, Laura; Roma, P.; Catapano, Alberico L.

doi:10.1515/cclm.2000.023

Cited by 17 publications

(11 citation statements)

References 29 publications

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“…In fact covalent alterations of LDL by acetylation, oxidation or glycation, increase lipoprotein uptake and cholesterol deposition within cultured cells. Moreover oxidized or glycated LDL induce lipid peroxidation in cultured cells [Colaco and Roser, 1994;Pirillo et al, 2000;Salvayre et al, 2002].…”

Section: Discussionmentioning

confidence: 99%

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Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells

Ferretti

Bacchetti

Moroni

et al. 2004

J of Cellular Biochemistry

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Homocysteine-thiolactone (HcyT) is a toxic product whose synthesis is directly proportional to plasma homocysteine (Hcy) levels. Previous studies demonstrated that the interaction between HcyT and low density lipoproteins (LDL) induces the formation of homocystamide-LDL adducts (Hcy-LDL). Structural and functional alterations of Hcy-LDL have been described and it has been suggested that homocysteinylation could increase atherogenicity of LDL. Oxidative damage of endothelial cells (EC) is considered to be a critical aspect of the atherosclerotic process. To further investigate the molecular mechanisms involved in the atherogenicity of homocysteinylated LDL, we studied the effect of interaction between Hcy-LDL and EC on cell oxidative damage, using human aortic endothelial cells (HAEC) as experimental model. Homocysteinylation of LDL was carried out by incubation of LDL, isolated from plasma of healthy normolipemic subjects, with HcyT (10-100 microM). In our experimental conditions, homocysteinylation treatment was not accompanied by oxidative damage of LDL. No modifications of apoprotein structure and physico-chemical properties were observed in Hcy-LDL with respect to control LDL (c-LDL), as evaluated using the intrinsic fluorescence of tryptophan and the probe Laurdan incorporated in lipoproteins. Our results demonstrated that Hcy-LDL incubated at 37 degrees C for 3 h with HAEC, induced an oxidative damage on human EC with a significant increase of lipid hydroperoxides in cells incubated with Hcy-LDL with respect to cell incubated with c-LDL. The compositional changes were associated with a significant decrease viability in cells treated with Hcy-LDL. The relationship between the levels of -SH groups of LDL and the oxidative damage of HAEC has been demonstrated. These results suggest that Hcy-LDL exert a cytotoxic effect that is likely related to an increase in lipid peroxidation and oxidative damage of EC.

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Section: Discussionmentioning

confidence: 99%

“…Alterations of functions and oxidative damages, induced by interactions with oxidized or glycated LDL on vascular endothelial cell, represent the early stages of the development of atherogenesis [Colaco and Roser, 1994;Khan et al, 1995;Pirillo et al, 2000;Salvayre et al, 2002].…”

mentioning

confidence: 99%

Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells

Ferretti

Bacchetti

Moroni

et al. 2004

J of Cellular Biochemistry

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“…Unlike members of the 60 kDa family, which have been identified as the culprit autoantigens in the development of early atherosclerosis, to date there is little evidence that other hsps, including hsp70 can induce atherosclerosis. [21] It seems that overexpression of hsp70 at the site of vessel injury and atherosclerotic lesion [30,31,33,34,36] has a cytoprotective role. [46,47] This is supported by the findings of Zhu et al [48] who demonstrated that human endothelial cells express hsp70 in response to oxidized LDL only when they proliferate, thus increasing the chance of survival of rapidly proliferating cells in the lesionprone areas.…”

Section: Discussionmentioning

confidence: 99%

“…[29] The role of immunity against hsp70 in atherosclerosis is less evaluated, although many studies demonstrated that hsp70 expression is higher at sites of atherosclerotic lesions than in normal tissue, [30][31][32][33] which can be at least in part the consequence of different stressful stimuli to the vessel wall. Pirillo et al [34] found that oxidized low-density lipoprotein (LDL) induce the synthesis of hsp70 in cultured human endothelial cells, while Xu et al [35] demonstrated hsp70 expression of vascular smooth muscle cells in response to nitric oxide. Balloon angioplasty and tobacco smoking was also shown to induce hsp70 expression in human blood vessels.…”

Section: Introductionmentioning

confidence: 99%

ANTIBODIES AGAINST THE HUMAN HEAT SHOCK PROTEIN hsp70 IN PATIENTS WITH SEVERE CORONARY ARTERY DISEASE

Kocsis

Veres

Vatay

et al. 2002

Immunological Investigations

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Heat shock proteins (hsps) play complex role in the function of the immune system, they can activate both humoral and cellular immune response, as well the complement system. Although autoimmunity to hsp70 was implicated in certain autoimmune diseases and other conditions, the exact role of anti-hsp70 antibodies is not known. It was demonstrated by our previous work and other's findings that antibodies against the 60 kDa hsps are strongly associated with coronary atherosclerosis and carotis disease. It is also known that there is increased hsp70 expression at different sites of atherosclerosis. Therefore our aim was to study whether level of anti-hsp70 antibodies correlate with the presence of severe coronary artery disease (CAD). We measured and compared anti-hsp70 IgG antibody levels in CAD patients (n = 99) and healthy subjects (n = 99) with ELISA. The frequency of these antibodies was high in both groups and there was no significant difference in the median level of anti-hsp70 antibodies between patients with severe CAD and controls (653 (400-1141) vs. 630 (326-1152) AU/mL, P = 0.337). Adjustment for age, sex, BMI and lipid parameters did not change this result. Furthermore we did not find a correlation between anti-hsp70 antibody levels and certain risk factors of CAD (age, lipid parameters, body mass index, C-reactive protein, gender, smoking, diabetes and anti-hsp60 antibodies). By contrast, in accordance with our previous findings, anti-hsp60 and anti-hsp65 antibody levels were significantly higher in CAD patients, compared to this control group (p < 0.0001 for both variables). We did not find any correlation between the levels of anti-hsp70 and anti-hsp60 or anti-hsp65 antibodies either in the patients or the controls. The exact role of hsp70 in atherosclerosis is controversial, but we suggest that humoral immunity against human hsp70 does not contribute to coronary atherosclerosis in contrast to antibodies against 60kDa hsps.

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“…It is commonly accepted that modified LDLs are important for early atherosclerosis initiation and progression (39,43). Endothelial dysfunction is often considered as one of the early predominant stages in atherosclerosis development (13).…”

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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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Oxidized Lipoproteins and Endothelium

Cited by 17 publications

References 29 publications

Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells

Effect of homocysteinylation of low density lipoproteins on lipid peroxidation of human endothelial cells

ANTIBODIES AGAINST THE HUMAN HEAT SHOCK PROTEIN hsp70 IN PATIENTS WITH SEVERE CORONARY ARTERY DISEASE

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

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