Adipose tissue arachidonic acid content is associated with the expression of 5-lipoxygenase in atherosclerotic plaques.
BACKGROUND
The content of arachidonic acid in adipose tissue is positively associated with the risk of myocardial infarction, whereas the content of eicosapentaenoic acid in adipose tissue has been reported to be negatively associated with the risk of myocardial infarction. Both arachidonic acid and eicosapentaenoic acid are substrates for the synthesis of pro-inflammatory leukotrienes and leukotrienes derived from eicosapentaenoic acid are generally much less potent. In this study we hypothesized that a high content of arachidonic acid in adipose tissue would reflect a high formation of arachidonic acid derived leukotrienes and a high expression of 5-lipoxygenase in atherosclerotic plaques. Likewise, we hypothesized that a high content of eicosapentaenoic acid in adipose tissue would reflect a low formation of arachidonic acid derived leukotrienes and a low expression of 5-lipoxygenase in plaques.


METHODS
In a cross sectional study we included 45 consecutive subjects undergoing femoral thrombendarterectomy. The expression of 5-lipoxygenase in plaques was assessed by a semi-automated image analysis computer programme after immunohistochemical staining with mono-clonal 5-lipoxygenase antibodies. Leukotriene B4 and cysteinyl leukotriene formation from stimulated femoral artery plaques was quantified using ELISA methods. The fatty acid content of adipose tissue biopsies from the thigh was analyzed using gas chromatography. Associations between variables were assessed by Pearson correlations and were further explored in a multivariable linear regression model adjusting for potential confounders.


RESULTS
A high content of arachidonic acid in adipose tissue was associated with a higher expression of 5-lipoxygenase in plaques (r = 0.32, p = 0.03), but no significant associations with leukotriene B4 (r = 0.22, p = 0.14) and cysteinyl leukotriene (r = -0.11, p = 0.46) formation was seen. No significant associations were found between the content of eicosapentaenoic acid in adipose tissue and 5-lipoxygenase expression or leukotriene formation in plaque.


CONCLUSIONS
Adipose tissue arachidonic acid contents correlated positively with the expression of 5-lipoxygenase in plaques. This association might represent a causal link between adipose tissue arachidonic acid and the risk of myocardial infarction but confirmatory studies are needed.
Department of Cardiology, Center for Cardiovascular Research, Aalborg University Hospital, Soendre Skovvej 15, 9000, Aalborg, Denmark. mrsn@rn.dk
Michael S
MS
Nielsen
Marie-Louise M
ML
Grønholdt
Mogens
M
Vyberg
Kim
K
Overvad
Annette
A
Andreasen
Karen-Margrete
KM
Due
Erik B
EB
Schmidt
D000273:Adipose Tissue / Q000378:metabolism* / Q000473:pathology; D000368:Aged; D000369:Aged, 80 and over; D001094:Arachidonate 5-Lipoxygenase / Q000235:genetics* / Q000378:metabolism; D016718:Arachidonic Acid / Q000378:metabolism*; D003430:Cross-Sectional Studies; D015118:Eicosapentaenoic Acid / Q000378:metabolism*; D005260:Female; D005263:Femoral Artery / Q000378:metabolism* / Q000473:pathology; D015870:Gene Expression; D006801:Humans; D007975:Leukotriene B4 / Q000378:metabolism; D015289:Leukotrienes / Q000378:metabolism; D008297:Male; D008875:Middle Aged; D058226:Plaque, Atherosclerotic / Q000235:genetics* / Q000378:metabolism / Q000473:pathology; D017131:Thrombectomy
D015289:Leukotrienes; D007975:Leukotriene B4; D016718:Arachidonic Acid; D015118:Eicosapentaenoic Acid; D001094:Arachidonate 5-Lipoxygenase