Potency of arachidonic acid in polyunsaturated fatty acid-induced death of human monocyte-macrophages: implications for atherosclerosis.
Evidence suggests that oxidation of LDL is involved in the progression of atherosclerosis by inducing apoptosis in macrophages. Polyunsaturated fatty acids (PUFAs) are prominent components of LDL and are highly peroxidisable. We therefore tested PUFAs for induction of apoptosis in human monocyte-macrophages in vitro. Arachidonic acid (AA) induced the highest levels of apoptosis followed by docosahexaenoic acid (DHA) and eicosapentaenoic acid (EPA), despite DHA and EPA being more peroxidisable than AA. alpha-Linolenic acid induced lower levels of apoptosis. Linoleic and oleic acids were innocuous. Results of experiments with AA products and enzyme inhibitors suggest roles for peroxidation, cyclooxygenase and lipoxygenase in AA-induced apoptosis. Our results further suggest activation of PPARgamma by AA and DHA associated with apoptosis induction. These findings may be relevant to potential mechanisms of fatty acid influences on plaques and may suggest strategies for combating atherosclerosis progression.
Department of Pathology, University of Cambridge, Tennis Court Road, Cambridge CB2 1QP, UK.
Balaji
B
Muralidhar
Keri L H
KL
Carpenter
Karin
K
Müller
Jeremy N
JN
Skepper
Mark J
MJ
Arends
D017209:Apoptosis / Q000187:drug effects*; D016718:Arachidonic Acid / Q000378:metabolism / Q000494:pharmacology*; D001161:Arteriosclerosis / Q000378:metabolism / Q000473:pathology*; D002478:Cells, Cultured; D016861:Cyclooxygenase Inhibitors / Q000494:pharmacology; D006801:Humans; D015227:Lipid Peroxidation; D016859:Lipoxygenase Inhibitors / Q000494:pharmacology; D008264:Macrophages / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology* / Q000648:ultrastructure; D046529:Microscopy, Electron, Transmission; D009000:Monocytes / Q000166:cytology* / Q000187:drug effects* / Q000378:metabolism / Q000648:ultrastructure; D047495:PPAR gamma / Q000378:metabolism
D016861:Cyclooxygenase Inhibitors; D016859:Lipoxygenase Inhibitors; D047495:PPAR gamma; D016718:Arachidonic Acid