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Adipose tissue arachidonic acid content is associated with the expression of 5-lipoxygenase in atherosclerotic plaques

Authors: Michael Nielsen; Marie-Louise M. Grønholdt; Mogens Vyberg; Annette Andreasen; Erik Berg Schmidt; Karen Margrete Due; Kim Overvad; +1 Authors

Adipose tissue arachidonic acid content is associated with the expression of 5-lipoxygenase in atherosclerotic plaques

Abstract

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.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.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.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.

Country
Denmark
Keywords

Male, Cysteinyl leukotrienes, Leukotrienes, Eicosapentaenoic acid, RC620-627, Atherosclerotic plaques, Endocrinology, Diabetes and Metabolism, Clinical Biochemistry, Adipose tissue, Gene Expression, Leukotriene B4, Leukotriene B<sub>4</sub>, Endocrinology, Humans, Nutritional diseases. Deficiency diseases, Aged, Thrombectomy, 5-Lipoxygenase, Biochemistry, medical, Aged, 80 and over, Arachidonate 5-Lipoxygenase, Arachidonic Acid, Research, Middle Aged, Plaque, Atherosclerotic, Femoral Artery, Cross-Sectional Studies, Arachidonic acid, Adipose Tissue, Eicosapentaenoic Acid, Female

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citations
This is an alternative to the "Influence" indicator, which also reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Citations provided by BIP!
popularity
This indicator reflects the "current" impact/attention (the "hype") of an article in the research community at large, based on the underlying citation network.
BIP!Popularity provided by BIP!
influence
This indicator reflects the overall/total impact of an article in the research community at large, based on the underlying citation network (diachronically).
BIP!Influence provided by BIP!
impulse
This indicator reflects the initial momentum of an article directly after its publication, based on the underlying citation network.
BIP!Impulse provided by BIP!
6
Average
Average
Average
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gold