Trans-fatty acids induce pro-inflammatory responses and endothelial cell dysfunction.
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.
Harvey
Kevin A
KA
Cellular Biochemistry Laboratory, Methodist Research Institute, Clarian Health, 1701 N. Senate - Room E504, Indianapolis, IN 46202, USA.
Arnold
Tyler
T
Rasool
Tamkeen
T
Antalis
Caryl
C
Miller
Steven J
SJ
Siddiqui
Rafat A
RA
D015415:Biomarkers / Q000032:analysis; D002196:Capillaries / Q000166:cytology / Q000187:drug effects; D002448:Cell Adhesion / Q000187:drug effects; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D018932:Chemokine CCL2 / Q000032:analysis; D002634:Chemotaxis, Leukocyte / Q000187:drug effects; D042783:Endothelial Cells / Q000166:cytology / Q000276:immunology / Q000378:metabolism*; D005434:Flow Cytometry; D006801:Humans; D039302:Integrin alphaVbeta3 / Q000032:analysis; D018799:Intercellular Adhesion Molecule-1 / Q000032:analysis; D008246:Lysophospholipids / Q000494:pharmacology; D009000:Monocytes / Q000187:drug effects; D009504:Neutrophils / Q000187:drug effects; D013110:Sphingosine / Q000031:analogs & derivatives / Q000494:pharmacology; D044242:Trans Fatty Acids / Q000378:metabolism / Q000494:pharmacology*
D015415:Biomarkers; C111835:CCL2 protein, human; D018932:Chemokine CCL2; D039302:Integrin alphaVbeta3; D008246:Lysophospholipids; D044242:Trans Fatty Acids; D018799:Intercellular Adhesion Molecule-1; C060506:sphingosine 1-phosphate; D013110:Sphingosine