British Journal of Nutrition

Full Papers

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

Kevin A. Harveya1, Tyler Arnolda1, Tamkeen Rasoola1, Caryl Antalisa1, Steven J. Millera2 and Rafat A. Siddiquia1a3a4 c1

a1 Cellular Biochemistry Laboratory, Methodist Research Institute, Clarian Health, 1701 N. Senate – Room E504, Indianapolis, IN 46202, USA

a2 Department of Surgery, Indiana University School of Medicine, Indianapolis, IN, USA

a3 Department of Biology, Indiana University-Purdue University, Indianapolis, IN, USA

a4 Department of Medicine, Indiana University School of Medicine, Indianapolis, IN, USA

Abstract

Epidemiological data indicate that there is a strong association between intake of trans-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 present in vitro study 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 of cis-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 on in vitro angiogenic 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, these in vitro studies demonstrated that TFA play a role in the induction of pro-inflammatory responses and endothelial cell dysfunction.

(Received January 19 2007)

(Revised July 13 2007)

(Accepted July 16 2007)

Correspondence:

c1 Corresponding author: Dr Rafat Siddiqui, fax +1 317 962 9369, email rsiddiqu@clarian.org

Footnotes

Abbreviations: EBM-2, endothelial cell basal medium-2; HAEC, human aortic endothelial cells; MCP-1, monocyte chemoattractant protein-1; SPP, sphingosine-1-phosphate