Cytotoxic effects of the lipid peroxidation product 2,4-decadienal in vascular smooth muscle cells.
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.
Cabré
Anna
A
Unitat de Recerca de Lípids i Arteriosclerosi - Fundació IRCIS, Facultat de Medicina, Universitat Rovira i Virgili, C. Sant Llorenç 21, 43201 Reus, Spain.
Girona
Josefa
J
Vallvé
Joan-C
JC
Heras
Mercedes
M
Masana
Lluís
L
D000447:Aldehydes / Q000633:toxicity*; D053938:DNA Fragmentation; D015870:Gene Expression / Q000187:drug effects; D016259:Genes, myc / Q000187:drug effects; D016158:Genes, p53 / Q000187:drug effects; D007770:L-Lactate Dehydrogenase / Q000378:metabolism; D032342:Muscle Cells / Q000166:cytology / Q000187:drug effects; D009131:Muscle, Smooth, Vascular / Q000187:drug effects*; D012333:RNA, Messenger / Q000032:analysis; D020133:Reverse Transcriptase Polymerase Chain Reaction
D000447:Aldehydes; D012333:RNA, Messenger; C057349:2,4-decadienal; C010463:n-hexanal; D007770:L-Lactate Dehydrogenase