Palmitate-induced interleukin-6 expression in human coronary artery endothelial cells.
Obesity-linked insulin resistance is associated with chronic inflammation and cardiovascular complications. Free fatty acids (FFAs) are prominent candidates for the molecular link between these disorders. In this study, we determined whether FFAs contribute to vascular inflammation via induction of interleukin (IL)-6 in coronary artery endothelial cells (CAECs) and coronary artery smooth muscle cells (CASMCs) and whether this is reflected in vivo. In contrast to our findings regarding IL-6 and gp130 (the glycoprotein of 130 kDa) expression, IL-6 receptor mRNA expression was very low in these cells. Palmitate, but not linoleate, induced a significant increase in IL-6 mRNA expression in CAECs (P < 0.001) and, to a less relevant extent, in CASMCs (P < 0.01). gp130 remained unaffected. As to potency, palmitate was comparable with the IL-6-inducer IL-1beta. To substantiate our in vitro data, we examined the plasma FFA pattern in 54 healthy human subjects and studied the relation of individual FFAs with plasma IL-6. IL-6 levels correlated with palmitate, but not with other abundant FFAs, even after adjusting for body fat (r = 0.33, P < 0.05) and total FFAs (r = 0.29, P < 0.05). We show here that the common plasma FFA palmitate induces high levels of IL-6 in CAECs. Furthermore, palmitate correlates with IL-6 in vivo. This points to a potential contribution of palmitate to vascular inflammation.
Staiger
Harald
H
Department of Endocrinology, Metabolism and Pathobiochemistry, Medical Clinic, Eberhard-Karls-University, Tübingen, Germany.
Staiger
Katrin
K
Stefan
Norbert
N
Wahl
Hans Günther
HG
Machicao
Fausto
F
Kellerer
Monika
M
Häring
Hans-Ulrich
HU
D000328:Adult; D003331:Coronary Vessels / Q000187:drug effects / Q000276:immunology*; D016207:Cytokines / Q000097:blood; D004730:Endothelium, Vascular / Q000187:drug effects / Q000276:immunology*; D005230:Fatty Acids, Nonesterified / Q000097:blood; D005260:Female; D005786:Gene Expression Regulation / Q000187:drug effects*; D006801:Humans; D015850:Interleukin-6 / Q000235:genetics*; D008297:Male; D019308:Palmitic Acid / Q000494:pharmacology*; D012333:RNA, Messenger / Q000235:genetics; D019947:Receptors, Interleukin-6 / Q000235:genetics; D012016:Reference Values
D016207:Cytokines; D005230:Fatty Acids, Nonesterified; D015850:Interleukin-6; D012333:RNA, Messenger; D019947:Receptors, Interleukin-6; D019308:Palmitic Acid