Document Detail


Atherogenic lipoproteins, oxidative stress, and cell death.
MedLine Citation:
PMID:  10412740     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
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.
Authors:
J Galle; K Heermeier; C Wanner
Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Kidney international. Supplement     Volume:  71     ISSN:  0098-6577     ISO Abbreviation:  Kidney Int. Suppl.     Publication Date:  1999 Jul 
Date Detail:
Created Date:  1999-09-15     Completed Date:  1999-09-15     Revised Date:  2008-01-22    
Medline Journal Info:
Nlm Unique ID:  7508622     Medline TA:  Kidney Int Suppl     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  S62-5     Citation Subset:  IM    
Affiliation:
Department of Medicine, University Hospital of Würzburg, Germany. j-c.galle@mail.uni-wuerzburg.de
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MeSH Terms
Descriptor/Qualifier:
Apoptosis / 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:
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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