Circulation, Vol 84, 1725-1731, Copyright © 1991 by American Heart Association
HA Lehr, C Hubner, B Finckh, D Nolte, U Beisiegel, A Kohlschutter and K Messmer
BACKGROUND. In vitro and in vivo experiments have demonstrated the role of
oxidatively modified low density lipoprotein (oxLDL) in eliciting
leukocyte/endothelium interaction during early atherogenesis. METHODS AND
RESULTS. In the present study we investigated the effect of dietary fish
oil on oxLDL-induced leukocyte/endothelium interaction using intravital
fluorescence microscopy in the dorsal skinfold chamber model in awake
Syrian golden hamsters. Hamsters were fed for 4 weeks prior to the
experiments with either standard laboratory chow or a diet supplemented
with 5% of a fish oil concentrate (18% eicosapentaenoate, 12%
docosahexaenoate). The efficacy of the fish oil diet was demonstrated by
the incorporation of fish oil-derived omega-3 fatty acids into plasma,
leukocyte, and erythrocyte lipids. In control hamsters (n = 7) and fish
oil-fed hamsters (n = 7), leukocyte/endothelium interaction was assessed in
the time course after intravenous injection of human LDL (4 mg/kg),
oxidized by 7.5 microM Cu2+ (6 hours, 37 degrees C). In control hamsters,
injection of oxLDL elicited the rolling and sticking of leukocytes to the
endothelium of arterioles and postcapillary venules with a maximum 15
minutes after injection (arterioles: from 3 +/- 1 to 91 +/- 25 cells/mm2 at
15 minutes; venules: from 13 +/- 6 to 150 +/- 46 cells/mm2 at 15 minutes;
mean +/- SD). This phenomenon was significantly reduced in fish oil-fed
hamsters, where 15 minutes after injection of oxLDL leukocyte sticking
reached a maximum of only 15 +/- 7 and 20 +/- 5 cells/mm2 in arterioles and
postcapillary venules, respectively (p less than 0.01 versus control
animals). CONCLUSIONS. The results of the present study suggest that
inhibition of leukocyte/endothelium interaction may be one of the
mechanisms by which dietary fish oil exerts its protective effects on
experimental and clinical atherogenesis.
ARTICLES
Dietary fish oil reduces leukocyte/endothelium interaction following systemic administration of oxidatively modified low density lipoprotein
Department of Experimental Surgery, University of Heidelberg, Germany.
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