British Journal of Nutrition

Full Papers

Human and Clinical Nutrition

n-3 Fatty acids prevent whereas trans-fatty acids induce vascular inflammation and sudden cardiac death

Rafat A. Siddiquia1a2 c1, Kevin A. Harveya1, Nargiz Ruzmetova1a2, Steven J. Millera3 and Gary P. Zalogaa4

a1 Cellular Biochemistry and Lipid Biology Laboratories, Methodist Research Institute E504D, 1800 N Capitol Avenue, Indianapolis, IN, USA

a2 Department of Medicine, Indiana University School of Medicine, 1120 South Drive, Indianapolis, IN, USA

a3 Department of Surgery, Indiana University School of Medicine, 1120 South Drive, Indianapolis, IN, USA

a4 Baxter Healthcare, One Baxter Parkway, Deerfield, IL, USA

Abstract

n-3 PUFA have well-recognised cardio-beneficial effects. In contrast, premature coronary deaths are associated with consumption of high levels of trans-fatty acids (TFA). The present study determined the effects of n-3 PUFA and TFA on sudden cardiac death and vascular inflammation. A rat coronary ligation model was used to study the effect of fatty acids on sudden cardiac death, whereas a mouse femoral artery ligation model was used to study compensatory vascular remodelling. Human aortic endothelial cells (HAEC) were utilised for the in vitro studies to investigate expression of inflammatory molecules. Feeding animals an n-3 PUFA-enriched diet caused a sevenfold increase in plasma n-3 PUFA compared with that of the TFA-fed group, whereas a TFA-enriched diet caused a 2·5-fold increase in plasma TFA compared with the n-3 PUFA group. Animals on a TFA diet had a lower survival rate due to sudden cardiac death and exhibited variable degrees of aortic atherosclerotic lesions. Animals on a TFA diet had diminished hindlimb collateral growth, whereas animals on the n-3 PUFA diet exhibited extensive collateral growth about ligated regions. HAEC treated with TFA (trans-18 : 2) showed significantly increased expression of intracellular adhesion molecule-1 and nitrosylation of cellular proteins than those treated with DHA (n-3 PUFA, 22 : 6). The in vivo study demonstrates that, in contrast to TFA, n-3 PUFA improve animal survival after myocardial infarction, prevent development of atherosclerotic lesions and stimulate compensatory vascular remodelling. The in vitro study demonstrates that TFA induce, while n-3 PUFA prevent, vascular inflammation.

(Received November 17 2008)

(Revised March 19 2009)

(Accepted April 23 2009)

(Online publication October 13 2009)

Correspondence:

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

Footnotes

Abbreviations: HDL-C, HDL cholesterol; ICAM-1, intercellular adhesion molecule-1; MI, myocardial infarction; sICAM-1, soluble ICAM-1; TFA, trans-fatty acids; VCAM-1, vascular cell adhesion molecule-1