Secretory Type II Phospholipase A2 Is Produced and Secreted by Epicardial Adipose Tissue and Overexpressed in Patients with Coronary Artery Disease

摘要

Context: Epicardial adipose tissue (EAT) is a visceral adipose tissue in close contact with coronary vessels, the excess of which is associated with coronary artery disease (CAD).Objective: Our goal was to identify candidate molecule(s) characterizing EAT that could intervene in the pathogenesis of CAD.Design: An approach combining microarrays and bioinformatic sequence analysis tools for predicting secreted proteins (TargetP) was applied to paired biopsies of sc adipose tissue (SAT) and EAT, obtained from patients with or without CAD (NCAD). Results were validated in three independent groups of subjects by quantitative RT-PCR, Western blot, immunohistochemistry, and explant secretion.Results: Secretory type II phospholipase A2 (sPLA2-IIA) ranked as the highest gene coding for potentially secreted proteins with the highest overexpression in EAT in both CAD and NCAD. Quantitative RT-PCR confirmed its increased expression in EAT ( P < 0.01) as well as EAT from CAD as compared with NCAD (49.3 ± 13 vs . 17.4 ± 9.7 P < 0.01). sPLA2-IIA protein levels were higher in EAT than SAT ( P < 0.001). EAT explants also showed significantly higher sPLA2-IIA secretion levels than SAT ones (4.37 ± 2.7 vs . 0.67 ± 0.28 ng/ml to 1 per gram tissue per 24 h, P < 0.03). sPLA2-IIA labeling was seen in the stroma vascular fraction between adipocytes and in connective capsules in EAT, with no immunostaining of the adipocytes. SAT was weakly labeled following the same process.Conclusion: We have shown for the first time an increased expression of sPLA2-IIA in EAT in patients with CAD. sPLA2-IIA is a phospholipase, which has been shown to be an independent risk factor for CAD. These findings suggest that EAT has a potentially pathophysiological role in CAD.