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

Lipids in Health and Disease

Erik B Schmidt³  Karen-Margrete Due³  Annette Andreasen³  Kim Overvad²  Mogens Vyberg¹  Marie-Louise M Grønholdt⁴  Michael S Nielsen³ 

[1] Institute of Pathology, Aalborg University Hospital, Ladegaardsgade 3, 9100, Aalborg, Denmark;Section for Epidemiology, Department of Public Health, Aarhus University, Bartholin Allé 2, 8000, Aarhus, Denmark;Department of Cardiology, Center for Cardiovascular Research, Aalborg University Hospital, Soendre Skovvej 15, 9000, Aalborg, Denmark;Department of Surgery, Nyborg Hospital, Vestergade 17, 5800, Nyborg, Denmark

关键词: Cysteinyl leukotrienes;    Leukotriene B₄;    5-Lipoxygenase;    Atherosclerotic plaques;    Eicosapentaenoic acid;    Arachidonic acid;    Adipose tissue;   

Others  :  1160098
DOI  :  10.1186/1476-511X-12-7

 received in 2013-01-06, accepted in 2013-01-22,  发布年份 2013

【 摘 要 】

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.

【 授权许可】

   
2013 Nielsen et al.; licensee BioMed Central Ltd.

【 图 表 】

Figure 1.

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