Differential Effects of Ruminant and Industrial 18-Carbon trans-Monounsaturated Fatty Acids (trans Vaccenic and Elaidic) on the Inflammatory Responses of an Endothelial Cell Line.

Philip C Calder,Carina A Valenzuela,Ella J Baker,Elizabeth A Miles,Camila O De Souza

doi:10.3390/molecules26195834

Abstract

Endothelial dysfunction and inflammation are recognised factors in the development of atherosclerosis. Evidence suggests that intake of industrial trans fatty acids (TFAs) promotes endothelial dysfunction, while ruminant TFAs may have the opposite effect. The aim of this study was to compare the effects of elaidic acid (EA (18:1n-9t); an industrially produced TFA) and trans vaccenic acid (TVA (18:1n-7t); a natural TFA found in ruminant milk and meat) on inflammatory responses of endothelial cells (ECs). ECs (EA.hy926 cells) were cultured under standard conditions and exposed to TFAs (1 to 50 μM) for 48 h. Then, the cells were cultured for a further 6 or 24 h with tumour necrosis factor alpha (TNF-α, 1 ng/mL) as an inflammatory stimulant. ECs remained viable after treatments. TFAs were incorporated into ECs in a dose-dependent manner. Preincubation with EA (50 µM) increased production of MCP-1, RANTES, and IL-8 in response to TNF-α, while preincubation with TVA (1 µM) decreased production of ICAM-1 and RANTES in response to TNF-α. Preincubation with EA (50 µM) upregulated toll-like receptor 4 and cyclooxygenase 2 gene expression in response to TNF-α. In contrast, preincubation with TVA (1 µM) downregulated TNF-α induced nuclear factor kappa B subunit 1 gene expression. Preincubation of ECs with EA (50 µM) increased THP-1 monocyte adhesion. In contrast, preincubation of ECs with TVA (1 µM) reduced THP-1 monocyte adhesion, while preincubation of ECs with TVA (50 µM) decreased the level of surface expression of ICAM-1 seen following TNF-α stimulation. The results suggest that TVA has some anti-inflammatory properties, while EA enhances the response to an inflammatory stimulus. These findings suggest differential effects induced by the TFAs tested, fitting with the idea that industrial TFAs and ruminant TFAs can have different and perhaps opposing biological actions in an inflammatory context.

Highlights

Coronary heart disease (CHD) and stroke are still the leading causes of death globally [1], and atherosclerosis has a key role in their pathogenesis
Neither TNF-α (1 ng/mL for 24 h) nor any of the four fatty acids (FAs) tested at concentrations of 1, 10, and 50 μM affected the viability of elaidic acid (EA).hy926 cells, as assessed using the 3-(4,5dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide (MTT) assay (Figure 1)
With the purpose of understanding the possible differential effects and mechanisms through which trans fatty acids (TFAs) could affect normal functioning of human endothelial tissues in relation to cardiovascular disease (CVD) development, the present study compared the effects of 18-carbon cis and trans FA isomers on the inflammatory response in cultured EA.hy926 endothelial cells (ECs)

Summary

Introduction

Coronary heart disease (CHD) and stroke are still the leading causes of death globally [1], and atherosclerosis has a key role in their pathogenesis. Endothelial dysfunction is a pro-inflammatory state characterised by chronic activation of the endothelium, which leads to atherosclerosis and cardiovascular disease (CVD). There are two different dietary sources of TFAs: the industrially produced TFAs (iTFAs) and the naturally occurring or ruminant TFAs (rTFAs). Given that partially hydrogenated vegetable oils can contain between 30 and 50% of iTFAs, mainly elaidic acid (EA; 18:1n-9t), while dairy and ruminant products only have between 2 and 6% of rTFAs (mostly trans vaccenic acid, (TVA; 18:1n-7t)), quantitatively the main dietary source of TFAs is usually partially hydrogenated vegetable oils [13]

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