Document Detail


Cytotoxic effects of the lipid peroxidation product 2,4-decadienal in vascular smooth muscle cells.
MedLine Citation:
PMID:  12921975     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
It is well known that oxidized LDL can be cytotoxic to smooth muscle cells (SMC) and then contribute to the progression of atherosclerosis. Nevertheless, which oxidized compound and which mechanism are involved in cell death is still under study. In this work we have studied the role of two representative apolar aldehydes (hexanal and 2,4-decadienal (2,4-DDE)), derived from polyunsaturated fatty acids oxidation, on human SMC cytotoxicity. Cell cytotoxicity was assessed by means of lactate deshydrogenase (LDH) release, cell morphology and DNA fragmentation. Results showed that hexanal up to 50 microM for 24 h was not cytotoxic to cells. However, 2,4-DDE at 50 microM for 24 h induced a 48% LDH leakage. The observed cytotoxic effect of 2,4-DDE was not due to a programmed cell death as no DNA ladder was detected. After aldehydes exposition a decreased expression of p53 and c-myc mRNA, genes involved in cell death regulation, was also demonstrated by RT-PCR. These observations suggest that 2,4-DDE may be the molecular cause of lipid oxidation cytotoxicity to human vascular SMC. By inducing cell necrosis in advanced stages, lipid oxidation may contribute to the cell debris core which is growing in the atherosclerotic lesion leading to a weakened and unstable plaque.
Authors:
Anna Cabré; Josefa Girona; Joan-C Vallvé; Mercedes Heras; Lluís Masana
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Atherosclerosis     Volume:  169     ISSN:  0021-9150     ISO Abbreviation:  Atherosclerosis     Publication Date:  2003 Aug 
Date Detail:
Created Date:  2003-08-18     Completed Date:  2004-01-20     Revised Date:  2006-11-15    
Medline Journal Info:
Nlm Unique ID:  0242543     Medline TA:  Atherosclerosis     Country:  Ireland    
Other Details:
Languages:  eng     Pagination:  245-50     Citation Subset:  IM    
Affiliation:
Unitat de Recerca de Lípids i Arteriosclerosi - Fundació IRCIS, Facultat de Medicina, Universitat Rovira i Virgili, C. Sant Llorenç 21, 43201 Reus, Spain.
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MeSH Terms
Descriptor/Qualifier:
Aldehydes / toxicity*
DNA Fragmentation
Gene Expression / drug effects
Genes, myc / drug effects
Genes, p53 / drug effects
L-Lactate Dehydrogenase / metabolism
Muscle Cells / cytology,  drug effects
Muscle, Smooth, Vascular / drug effects*
RNA, Messenger / analysis
Reverse Transcriptase Polymerase Chain Reaction
Chemical
Reg. No./Substance:
0/Aldehydes; 0/RNA, Messenger; 2363-88-4/2,4-decadienal; 66-25-1/n-hexanal; EC 1.1.1.27/L-Lactate Dehydrogenase

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