QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text (PDF) Purchase Article View Shopping Cart Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Fleet, J. C. Articles by Libby, P. Search for Related Content PubMed PubMed Citation Articles by Fleet, J. C. Articles by Libby, P.

Atherogenic Diets Enhance Endotoxin-Stimulated Interleukin-1 and Tumor Necrosis Factor Gene Expression in Rabbit Aortae^1,2,

James C. Fleet^*, Steven K. Clinton^*,3, Robert N. Salomon^*,,, Harald Loppnow^* and Peter Libby^**,4

^* U.S. Department of Agriculture Human Nutrition Research Center on Aging Department of Pathology, Tufts University ^** The Vascular Medicine and Atherosclerosis Unit, Brigham and Women's Hospital and Harvard Medical School, Boston, MA 02111

Cytokine-induced vascular changes may contribute to the atherogenic process. We examined the effect of atherogenic diets on the aortic expression of genes for the cytokines interleukin-1 and ß and tumor necrosis factor . Male New Zealand White rabbits were fed one of the following diets for 10 wk: nonpurified diet, a semipurified diet with 10% corn oil, a semipurified diet with 1% corn oil and 9% partially hydrogenated coconut oil, or the 9% coconut oil diet supplemented with either 0.1, 0.3 or 0.9% added cholesterol (n = 6/group). At 10 wk, 3 rabbits per group received lipopolysaccharide (200 µg/kg) intravenously. After 1.5 h the rabbits were killed and their aortae removed and analyzed. Histologic examination showed that the 0.3% and 0.9% cholesterolfed rabbits developed appreciable aortic lesions. Diet had no major effect on the basal levels of aortic cytokine mRNA as determined by polymerase chain reaction analysis of DNAs. However, aortic tissue from rabbits fed 0.3% and 0.9% cholesterol diets showed significantly enhanced lipopolysaccharide-evoked levels of mRNA encoding interleukin-1 (392 ± 91 for saturated fat vs. 759 ± 191 and 800 ± 120 fmoles/reaction for 0.3% and 0.9% cholesterol), interleukin-1ß (99 ± 10 vs. 353 ± 80 and 355 ± 86) and tumor necrosis factor (195 ± 15 vs. 594 ± 78 and 667 ± 97). Extracts of aortae from rabbits injected with lipopolysaccharide contained interleukin-1 and tumor necrosis factor activity but differences in biological activity due to diet were not detectable at the 1.5 h time point (chosen for maximal mRNA expression). Increased local cytokine gene expression in response to acute stimulus might influence the evolution of the vascular response to diets rich in cholesterol and saturated fats.

KEY WORDS: • rabbits • polymerase chain reaction • apolipoprotein E • cytokines

¹ Funded in part with federal funds from the U.S. Department of Agriculture, Agricultural Research Service under contract number 53-3K06-5-10. The contents of this publication do not necessarily reflect the views or policies of the U.S. Department of Agriculture, nor does mention of trade names, commercial products, or organizations imply endorsement by the U.S. Government. This work was accomplished while James Fleet was the Samuel A. Levine Fellow of the American Heart Association, Massachusetts Affiliate, Inc.

² Some of the data contained in this report were presented at the 1990 Annual Meeting of the American Institute of Nutrition, Washington, DC [Fleet, J., Clinton, S., Salomon, R., Loppnow, H. & Libby, P. (1990) Atherogenic diets increase endotoxin-stimulated cytokine gene expression in rabbit aortae. FASEB J. 4: A1156].

³ Current address: Dana Farber Cancer Institute, Harvard Medical School, 44 Binney St., Boston, MA 02117.

⁴ To whom correspondence and reprint requests should be addressed at The Vascular Medicine and Atherosclerosis Unit, Brigham and Women's Hospital and Harvard Medical School, 75 Francis St., Boston, MA 02111.

Manuscript received 26 October 1990. Revision accepted 31 July 1991.

This article has been cited by other articles:

				C. J. Wiedermann, S. Kiechl, S. Dunzendorfer, P. Schratzberger, G. Egger, F. Oberhollenzer, and J. Willeit Association of endotoxemia with carotid atherosclerosis and cardiovascular disease: Prospective results from the bruneck study J. Am. Coll. Cardiol., December 1, 1999; 34(7): 1975 - 1981. [Abstract] [Full Text] [PDF]

				J. F. Carlquist Endotoxin: another phantom menace? J. Am. Coll. Cardiol., December 1, 1999; 34(7): 1982 - 1984. [Full Text] [PDF]