Searchable abstracts of presentations at key conferences in endocrinology
Endocrine Abstracts (2015) 37 EP384 | DOI: 10.1530/endoabs.37.EP384

ECE2015 Eposter Presentations Diabetes (pathiophysiology & epitemiology) (80 abstracts)

TRAIL downregulates endothelin 1 and upregulates superoxide dismutase 1 in human aortic endothelial cells under pro-atherorgenic conditions

Hannah Forde 1, , Colin Davenport 1 , Diarmuid Smith 1 & Phil Cummins 2

1Beaumont Hospital, Beaumont, Dublin 9, Ireland; 2Dublin City University, Glasnevin, Dublin 9, Ireland.

Introduction: Increased oxidative stress is associated with endothelial dysfunction in atherosclerosis and cardiovascular diseases (CVD). Evidence suggests that tumour necrosis factor-related apoptosis-inducing ligand (TRAIL), a member of the tumour necrosis factor (TNF) superfamily, may also be involved in the pathogenesis of CVD. Observational studies have demonstrated that serum levels of TRAIL are inversely correlated with severity of coronary artery disease. This concurs with other recent in vivo findings suggesting that TRAIL may exhibit vasoprotective effects towards the endothelium, although the mechanism of TRAIL-mediated vasoprotection remains poorly understood. The aim of this study therefore was to characterise the effect of TRAIL on inflammatory gene expression from vascular endothelial cells in vitro under oscillatory flow, an essential component of atherosclerotic plaque formation.

Methods: Primary-derived human aortic endothelial cells (HAECs) were exposed to pathological oscillatory shear stress (±10 dyns/cm3) using the IBIDIR μslide perfusion unit in the presence and absence of recombinant human TRAIL (100 ng/ml, 24 h). RNA was isolated from the cells using a modified Mirvana method. Gene expression was assessed by a PCR array using qPCR.

Results: TRAIL downregulated expression of endothelin 1 (EDN1) gene, which encodes the proinflammatory cytokine EDN1. EDN1 is also associated with reactive oxygen species formation. TRAIL upregulated expression of superoxide dismutase 1 (SOD) gene, which encodes the potent antioxidant enzyme SOD1.

Conclusion: TRAIL exerts an anti-inflammatory effect on the endotheium under pro-atherogenic conditions, at least in part through reduction of oxidative stress.

Disclosure: This work was supported by the Basic Science Grant, received from the Irish Endocrine Society November 2013.

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