© 2000 American Heart Association, Inc.
Vascular Biology |
Accumulation of LDL in Rat Arteries Is Associated With Activation of Tumor Necrosis Factor-
Expression
From the Department of Medicine, Malmö University Hospital, Univerity of Lund, Malmö, Sweden
Correspondence to Jan Nilsson, Department of Medicine, Malmö University Hospital, 205 02 Malmö, Sweden. E-mail jan.nilsson{at}medforsk.mas.lu.se
Abstract—Activation of vascular
inflammation in response to hyperlipidemia is believed
to play an important role during the early stages of atherogenesis. We
demonstrate here that exposure of cultured, rat aortic smooth muscle
cells to low density lipoprotein (LDL) stimulated tumor necrosis
factor-
(TNF-) mRNA and protein expression. Oxidative
modification of LDL resulted in a reduction of this stimulatory effect.
To analyze whether a similar response also occurs in vivo, we
used a recently developed model in which the effects of a rapid
accumulation of human LDL in rat arteries can be studied. As previously
reported, epitopes specific for human apolipoprotein B began to
accumulate in the aorta within 2 to 6 hours after injection of 6 mg of
human LDL. This was followed by expression of oxidized LDL–specific
epitopes after 12 hours. There was no vascular expression of TNF- at
baseline or in phosphate-buffered saline–injected control rats.
However, 24 hours after injection of native LDL, there was a marked
induction of TNF- mRNA and immunoreactivity in the aorta and other
large arteries, whereas injection of oxidized LDL was without effect in
this respect. Preincubation of LDL with the antioxidant probucol before
injection markedly decreased the expression of TNF-
immunoreactivity. The present findings support the notion that LDL
may activate arterial expression of TNF- and
suggest 1 possible mechanism for the inflammatory response in the early
stages of atherosclerosis. The role of LDL oxidation in
this process remains to be fully elucidated.
Key Words: atherosclerosis • oxidized LDL • probucol • TNF-
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