| Atherogenic lipoproteins, oxidative stress, and cell death. | |
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MedLine Citation:
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PMID: 10412740 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Glomerulosclerosis and atherosclerosis are chronic inflammatory processes that may be influenced by oxidized lipoproteins, oxidized low-density lipoproteins (oxLDL), and oxidized lipoprotein(a) [oxLp(a)]. We hypothesize that these lipoproteins contribute to the development of glomerulosclerosis and atherosclerosis through the induction of oxidative stress, which influences cell viability. We therefore determined the impact of oxLDL and oxLp(a) on O2- formation and on necrotic and apoptotic cell death in vascular and glomerular cells. METHODS: The impact of human LDL and Lp(a) (oxidized with CuSO4) on O2- formation (detected with a chemiluminescence method), apoptosis, and necrosis (determined with the annexin assay) was studied in cultured human umbilical vein endothelial cells (ECs) and in cultured human mesangial cells (MCs). RESULTS: O2- formation was increased by 10 micrograms/ml oxLDL (by factor 2.5 in ECs) and by 5 micrograms/ml oxLp(a) (by factor 3.5 in ECs). OxLDL and oxLp(a) both significantly and dose-dependently increased the rate of apoptotic cell death in ECs and in MCs, with oxLp(a) being the more potent stimulus that also caused necrosis. The induction of apoptosis by oxLDL and oxLp(a) in ECs and MCs was enhanced by inhibition of the endogenous superoxide dismutase (SOD) with diethyl-dithio-carbamate and was blunted by the antioxidants N-acetylcysteine, vitamin C + E, SOD, and catalase, suggesting that oxidative stress was the stimulus for apoptosis. CONCLUSIONS: These data suggest that oxLDL and oxLp(a) contribute to inflammation by stimulating O2- formation, leading to apoptotic cell death in the vascular wall and in the glomerulus. The oxidized lipoproteins may thereby influence the pathogenesis of atherosclerosis and glomerulosclerosis. |
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Authors:
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J Galle; K Heermeier; C Wanner |
Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Kidney international. Supplement Volume: 71 ISSN: 0098-6577 ISO Abbreviation: Kidney Int. Suppl. Publication Date: 1999 Jul |
Date Detail:
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Created Date: 1999-09-15 Completed Date: 1999-09-15 Revised Date: 2008-01-22 |
Medline Journal Info:
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Nlm Unique ID: 7508622 Medline TA: Kidney Int Suppl Country: UNITED STATES |
Other Details:
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Languages: eng Pagination: S62-5 Citation Subset: IM |
Affiliation:
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Department of Medicine, University Hospital of Würzburg, Germany. j-c.galle@mail.uni-wuerzburg.de |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Apoptosis
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drug effects,
physiology Arteriosclerosis / etiology* Cell Death / drug effects*, physiology Cell Line Dose-Response Relationship, Drug Humans Lipoprotein(a) / metabolism, pharmacology Lipoproteins / metabolism, pharmacology* Lipoproteins, LDL / pharmacology Oxidation-Reduction Oxidative Stress* Reactive Oxygen Species / physiology |
| Chemical | |
Reg. No./Substance:
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0/Lipoprotein(a); 0/Lipoproteins; 0/Lipoproteins, LDL; 0/Reactive Oxygen Species; 0/oxidized low density lipoprotein |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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