Abstract
BackgroundThe 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.MethodsIn 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.ResultsA 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.ConclusionsAdipose 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.
Highlights
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
The marine omega-3 polyunsaturated fatty acid (PUFA), eicosapentaenoic acid (EPA) is generally considered to be beneficial in the prevention of coronary artery disease [1] whereas the n-6 PUFA, arachidonic acid (ARA), has been linked to a higher risk [2,3,4]. Both ARA and EPA serve as substrates for 5-lipoxygenase, the initiating enzyme in the biosynthesis of pro-inflammatory leukotrienes (Figure 1) and as described below, the leukotrienes derived from EPA are generally much less potent as compared to those derived from ARA
EPA can act as an alternative substrate, leading to the formation of 5-series leukotrienes (LTB5, LTC5, LTD5, LTE5) of which LTB5 is at least 30 times less potent in chemoattractant and aggregating properties compared to the ARA-derived Leukotriene B4 (LTB4) [6]
Summary
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. The marine omega-3 polyunsaturated fatty acid (PUFA), eicosapentaenoic acid (EPA) is generally considered to be beneficial in the prevention of coronary artery disease [1] whereas the n-6 PUFA, arachidonic acid (ARA), has been linked to a higher risk [2,3,4]. Both ARA and EPA serve as substrates for 5-lipoxygenase, the initiating enzyme in the biosynthesis of pro-inflammatory leukotrienes (Figure 1) and as described below, the leukotrienes derived from EPA are generally much less potent as compared to those derived from ARA. The cysteinyl leukotrienes, seem to possess potent biological activities regardless of the number of double bonds [7,8]
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