Trans-fatty acids induce pro-inflammatory responses and endothelial cell dysfunction

Abstract

Epidemiological data indicate that there is a strong association between intake oftrans-18 : 2 fatty acids (TFA) and sudden cardiac death. There is little known about the mechanisms by which TFA exert harmful effects on the cardiovascular system. The presentin vitrostudy is the first to demonstrate the effects of membrane-incorporated C18 : 2 TFA on human aortic endothelial cell (HAEC) function.Trans-18 : 2 fatty acids were incorporated to a greater extent (2-fold) in the phospholipid fraction of endothelial cells than that ofcis-18 : 2; furthermore, these fatty acids were enriched to a similar extent in the TAG fraction. Flow cytometric analysis indicated that TFA treatment of HAEC significantly increased the expression of endothelial adhesion molecules, including intercellular adhesion molecule-1 (CD54) and vitronectin receptor (CD51/CD61). Incorporation of TFA into membranes increased HAEC adhesion to fibronectin- or vitronectin-coated plates by 1·5- to 2-fold, respectively. Neutrophil and monocyte adhesion to HAEC monolayers was nearly proportional to adhesion molecule expression. TFA treatment also induced the release of monocyte chemoattractant protein-1 by nearly 3-fold in non-stimulated HAEC. Furthermore, we examined the role of TFA onin vitroangiogenic assays. Chemotactic migration of TFA-treated HAEC toward sphingosine-1-phosphate (SPP) was significantly increased compared with controls. Conversely, capillary morphogenesis of TFA-treated HAEC was significantly inhibited in response to SPP, suggesting that TFA incorporation suppresses endothelial cell differentiation. In conclusion, thesein vitrostudies demonstrated that TFA play a role in the induction of pro-inflammatory responses and endothelial cell dysfunction.