© 1999 American Heart Association, Inc.
Original Contributions |
Oleic Acid Inhibits Endothelial Activation
A Direct Vascular Antiatherogenic Mechanism of a Nutritional Component in the Mediterranean Diet
From the CNR Institute of Clinical Physiology, Lecce (M.A.C, M. Massaro, C.B.) and Pisa (A.D., R.D.C.), and the Department of Biology, University of Lecce (L.S., M. Maffia, G.N., C.S.), Lecce, Italy.
Correspondence to Raffaele De Caterina, MD, PhD, Laboratory for Thrombosis and Vascular Research, CNR Institute of Clinical Physiology, Via Savi, 8, I-56126 Pisa, Italy. E-mail rdecater{at}po.ifc.pi.cnr.it
Abstract—Because oleic acid is
implicated in the antiatherogenic effects attributed to the
Mediterranean diet, we investigated whether this fatty acid can
modulate endothelial activation, ie, the concerted
expression of gene products involved in leukocyte recruitment and
early atherogenesis. We incubated sodium oleate with human umbilical
vein endothelial cells for 0 to 72 hours, followed by
coincubation of oleate with human recombinant tumor necrosis factor,
interleukin (IL)-1
, IL-1ß, IL-4, Escherichia coli
lipopolysaccharide (LPS), or phorbol 12-myristate
13-acetate for a further 6 to 24 hours. The endothelial
expression of vascular cell adhesion molecule-1 (VCAM-1), E-selectin,
and intercellular adhesion molecule-1 was monitored by cell surface
enzyme immunoassays or flow cytometry, and steady-state levels of
VCAM-1 mRNA were assessed by Northern blot analysis. At 10 to
100 µmol/L for >24 hours, oleate inhibited the expression of
all adhesion molecules tested. After a 72-hour incubation with oleate
and a further 16-hour incubation with oleate plus 1 µg/mL LPS, VCAM-1
expression was reduced by >40% compared with control. Adhesion of
monocytoid U937 cells to LPS-treated endothelial cells
was reduced concomitantly. Oleate also produced a quantitatively
similar reduction of VCAM-1 mRNA levels on Northern blot
analysis and inhibited nuclear factor-
B activation on
electrophoretic mobility shift assays. Incubation of
endothelial cells with oleate for 72 hours decreased
the relative proportions of saturated (palmitic and stearic) acids in
total cell lipids and increased the proportions of oleate in total cell
lipids without significantly changing the relative proportions of
polyunsaturated fatty acids. Although less potent than polyunsaturated
fatty acids in inhibiting endothelial activation, oleic
acid may contribute to the prevention of atherogenesis through
selective displacement of saturated fatty acids in cell membrane
phospholipids and a consequent modulation of gene expression for
molecules involved in monocyte recruitment.
Key Words: fatty acids • endothelial activation • adhesion molecules • atherogenesis • nuclear factor-B
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