Comparative effects of fatty acids on endothelial inflammatory gene expression.
BACKGROUND
Endothelial dysfunction may be related to adverse effects of some dietary fatty acids (FAs). Although in vitro studies have failed to show consistent findings, this may reflect the diverse experimental protocols employed and the limited range of FAs and end points studied.


OBJECTIVE
To investigate the effect of dietary FA type (saturated, monounsaturated, n-6 and n-3 polyunsaturated fatty acids), concentration, incubation time and cell stimulation state, on a broad spectrum of endothelial inflammatory gene expression.


METHODS
Using human umbilical vein endothelial cells, with and without stimulation (+/-10 ng/ml TNFalpha), the effects of arachidonic (AA), docosahexaenoic (DHA), eicosapentaenoic (EPA), linoleic (LA), oleic (OA) and palmitic acids (PA) (10, 25 and 100 microM), on the expression of genes encoding a number of inflammatory proteins and transcription factors were assessed by quantitative real time RT-PCR.


RESULTS
Individual FAs differentially affect endothelial inflammatory gene expression in a gene-specific manner. EPA, LA and OA significantly up-regulated MCP-1 gene expression compared to AA (p = 0.001, 0.013, 0.008, respectively) and DHA (p < 0.0005, = 0.004, 0.002, respectively). Furthermore, cell stimulation state and FA incubation time significantly influenced reported FA effects on gene expression.


CONCLUSIONS
The comparative effects of saturated, monounsaturated, n-6 and n-3 polyunsaturated FAs on endothelial gene expression depend on the specific FA investigated, its length of incubation, cell stimulation state and the gene investigated. These findings may explain existing disparity in the literature.
Shaw
Danielle I
DI
Hugh Sinclair Unit of Human Nutrition, School of Food Biosciences, University of Reading, Reading, RG6 6AP, UK. d.i.shaw@reading.ac.uk
Hall
Wendy L
WL
Jeffs
Natasha R
NR
Williams
Christine M
CM
D002478:Cells, Cultured; D004041:Dietary Fats / Q000378:metabolism / Q000494:pharmacology*; D004042:Dietary Fats, Unsaturated / Q000378:metabolism / Q000494:pharmacology*; D042783:Endothelial Cells / Q000187:drug effects* / Q000378:metabolism; D005227:Fatty Acids / Q000378:metabolism / Q000494:pharmacology; D005229:Fatty Acids, Monounsaturated / Q000378:metabolism / Q000494:pharmacology; D005231:Fatty Acids, Unsaturated / Q000378:metabolism / Q000494:pharmacology; D015870:Gene Expression / Q000187:drug effects*; D006801:Humans; D012333:RNA, Messenger / Q000187:drug effects / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013997:Time Factors; D014471:Umbilical Veins / Q000166:cytology
D004041:Dietary Fats; D004042:Dietary Fats, Unsaturated; D005227:Fatty Acids; D005229:Fatty Acids, Monounsaturated; D005231:Fatty Acids, Unsaturated; D012333:RNA, Messenger
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