Effects of 7-ketocholesterol on the activity of endothelial poly(ADP-ribose) polymerase and on endothelium-dependent relaxant function

Levente Kiss, Min Chen, Domokos Gero, Katalin Módis, Zsombor Lacza, Csaba Szabó

Research output: Article

10 Citations (Scopus)

Abstract

Oxidative and nitrosative stress play an important role in the development of endothelial vascular dysfunction during early atherosclerosis. Oxidative stress activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in endothelial cells. In patients with atherosclerosis the level of oxidized LDL in the plasma is elevated. In oxidized LDL various oxysterols have been identified, such as 7-ketocholesterol (7K). 7K has been shown to induce PARP activation in microglial cells. The aim of the current study was to clarify the effects of 7K on the activity of endothelial PARP and on the endothelium-dependent relaxant function of blood vessels. We treated human umbilical vein endothelial (HUVEC) cells with 2-16 μg/ml 7K as well as vascular rings harvested from BALB/c mouse thoracic aorta with 90 μg/ml 7K for 2 h. A group of mice was treated with 7K subcutaneously for 1 week (10 mg/kg/day). We also conducted in vitro and in vivo experiments using pretreatment with buthionine sulphoximine (BSO), a glutathione-lowering agent. The activity of PARP was calculated by measurement of tritiated NAD incorporation. The activity of PARP increased significantly in 7K-treated HUVEC cells. After BSO pretreatment, this increase was higher. Isolated vascular rings demonstrated no change in endothelium-dependent relaxant function after 2 h of incubation with 7K, even after BSO pretreatment. In vivo treatment with 7K for 1 week had no effect on the relaxant function. Our experimental results suggest that although 7-ketocholesterol can activate PARP enzyme in endothelial cells, it is not sufficient on its own to cause impairment in the endothelium-dependent vascular reactivity.

Original languageEnglish
Pages (from-to)1113-1117
Number of pages5
JournalInternational Journal of Molecular Medicine
Volume18
Issue number6
Publication statusPublished - dec. 2006

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Poly(ADP-ribose) Polymerases
Endothelium
Buthionine Sulfoximine
Blood Vessels
Human Umbilical Vein Endothelial Cells
Atherosclerosis
Oxidative Stress
Endothelial Cells
7-ketocholesterol
Vascular Endothelium
Enzymes
Thoracic Aorta
NAD
Glutathione

ASJC Scopus subject areas

  • Genetics

Cite this

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title = "Effects of 7-ketocholesterol on the activity of endothelial poly(ADP-ribose) polymerase and on endothelium-dependent relaxant function",
abstract = "Oxidative and nitrosative stress play an important role in the development of endothelial vascular dysfunction during early atherosclerosis. Oxidative stress activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in endothelial cells. In patients with atherosclerosis the level of oxidized LDL in the plasma is elevated. In oxidized LDL various oxysterols have been identified, such as 7-ketocholesterol (7K). 7K has been shown to induce PARP activation in microglial cells. The aim of the current study was to clarify the effects of 7K on the activity of endothelial PARP and on the endothelium-dependent relaxant function of blood vessels. We treated human umbilical vein endothelial (HUVEC) cells with 2-16 μg/ml 7K as well as vascular rings harvested from BALB/c mouse thoracic aorta with 90 μg/ml 7K for 2 h. A group of mice was treated with 7K subcutaneously for 1 week (10 mg/kg/day). We also conducted in vitro and in vivo experiments using pretreatment with buthionine sulphoximine (BSO), a glutathione-lowering agent. The activity of PARP was calculated by measurement of tritiated NAD incorporation. The activity of PARP increased significantly in 7K-treated HUVEC cells. After BSO pretreatment, this increase was higher. Isolated vascular rings demonstrated no change in endothelium-dependent relaxant function after 2 h of incubation with 7K, even after BSO pretreatment. In vivo treatment with 7K for 1 week had no effect on the relaxant function. Our experimental results suggest that although 7-ketocholesterol can activate PARP enzyme in endothelial cells, it is not sufficient on its own to cause impairment in the endothelium-dependent vascular reactivity.",
keywords = "7-ketocholesterol, Atherosclerosis, Endothelial dysfunction, Poly(ADP-ribose) polymerase",
author = "Levente Kiss and Min Chen and Domokos Gero and Katalin M{\'o}dis and Zsombor Lacza and Csaba Szab{\'o}",
year = "2006",
month = "12",
language = "English",
volume = "18",
pages = "1113--1117",
journal = "International Journal of Molecular Medicine",
issn = "1107-3756",
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TY - JOUR

T1 - Effects of 7-ketocholesterol on the activity of endothelial poly(ADP-ribose) polymerase and on endothelium-dependent relaxant function

AU - Kiss, Levente

AU - Chen, Min

AU - Gero, Domokos

AU - Módis, Katalin

AU - Lacza, Zsombor

AU - Szabó, Csaba

PY - 2006/12

Y1 - 2006/12

N2 - Oxidative and nitrosative stress play an important role in the development of endothelial vascular dysfunction during early atherosclerosis. Oxidative stress activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in endothelial cells. In patients with atherosclerosis the level of oxidized LDL in the plasma is elevated. In oxidized LDL various oxysterols have been identified, such as 7-ketocholesterol (7K). 7K has been shown to induce PARP activation in microglial cells. The aim of the current study was to clarify the effects of 7K on the activity of endothelial PARP and on the endothelium-dependent relaxant function of blood vessels. We treated human umbilical vein endothelial (HUVEC) cells with 2-16 μg/ml 7K as well as vascular rings harvested from BALB/c mouse thoracic aorta with 90 μg/ml 7K for 2 h. A group of mice was treated with 7K subcutaneously for 1 week (10 mg/kg/day). We also conducted in vitro and in vivo experiments using pretreatment with buthionine sulphoximine (BSO), a glutathione-lowering agent. The activity of PARP was calculated by measurement of tritiated NAD incorporation. The activity of PARP increased significantly in 7K-treated HUVEC cells. After BSO pretreatment, this increase was higher. Isolated vascular rings demonstrated no change in endothelium-dependent relaxant function after 2 h of incubation with 7K, even after BSO pretreatment. In vivo treatment with 7K for 1 week had no effect on the relaxant function. Our experimental results suggest that although 7-ketocholesterol can activate PARP enzyme in endothelial cells, it is not sufficient on its own to cause impairment in the endothelium-dependent vascular reactivity.

AB - Oxidative and nitrosative stress play an important role in the development of endothelial vascular dysfunction during early atherosclerosis. Oxidative stress activates the nuclear enzyme poly(ADP-ribose) polymerase (PARP) in endothelial cells. In patients with atherosclerosis the level of oxidized LDL in the plasma is elevated. In oxidized LDL various oxysterols have been identified, such as 7-ketocholesterol (7K). 7K has been shown to induce PARP activation in microglial cells. The aim of the current study was to clarify the effects of 7K on the activity of endothelial PARP and on the endothelium-dependent relaxant function of blood vessels. We treated human umbilical vein endothelial (HUVEC) cells with 2-16 μg/ml 7K as well as vascular rings harvested from BALB/c mouse thoracic aorta with 90 μg/ml 7K for 2 h. A group of mice was treated with 7K subcutaneously for 1 week (10 mg/kg/day). We also conducted in vitro and in vivo experiments using pretreatment with buthionine sulphoximine (BSO), a glutathione-lowering agent. The activity of PARP was calculated by measurement of tritiated NAD incorporation. The activity of PARP increased significantly in 7K-treated HUVEC cells. After BSO pretreatment, this increase was higher. Isolated vascular rings demonstrated no change in endothelium-dependent relaxant function after 2 h of incubation with 7K, even after BSO pretreatment. In vivo treatment with 7K for 1 week had no effect on the relaxant function. Our experimental results suggest that although 7-ketocholesterol can activate PARP enzyme in endothelial cells, it is not sufficient on its own to cause impairment in the endothelium-dependent vascular reactivity.

KW - 7-ketocholesterol

KW - Atherosclerosis

KW - Endothelial dysfunction

KW - Poly(ADP-ribose) polymerase

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VL - 18

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JO - International Journal of Molecular Medicine

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