Abstract：
:Abundant data is present to implicate oxidatively modified low-density lipoprotein (oxLDL) in enhanced atherogenesis. Among the factors involved in LDL oxidation, an important role has been attributed to human 15-lipoxygenase (LO) and its murine analog 12-LO. The expression of these peroxidizing enzymes is under the control of cytokines, the principal of which is IL-4. In the present study we tested the hypothesis that knocking out the IL-4 gene from C57BL/6 mice would result in suppression of fatty streaks. For this purpose, we have fed 45 female IL-4 transgenic knockout (IL-4T KO) and 45 wild-type (WT) mice an atherogenic diet for 15 weeks. Consecutive determinations of the lipid profile from both study groups were performed at monthly intervals, and fatty streak formation was assessed at the aortic sinus level, upon sacrifice. The two study groups did not differ significantly with respect to the lipid profile or the uptake and degradation of iodinated oxLDL by their peritoneal macrophages. We found that the endogenous deficiency of IL-4 did not confer protection from early atherosclerosis in the IL-4T KO as compared to their WT littermates (determined at the aortic sinus). Immunohistochemical studies, Western blots and 12/15-LO activity assays revealed the presence and activity of 12/15-LO in macrophages of WT mice as well as in IL-4T KO mice. Both did not differ significantly between the study groups. The data from this study imply that deficiency in IL-4 does not affect early atherosclerosis in C57BL/6 mice fed a high-cholesterol diet.
journal_name
Atherosclerosisjournal_title
Atherosclerosisauthors
George J,Mulkins M,Shaish A,Casey S,Schatzman R,Sigal E,Harats Ddoi
10.1016/s0021-9150(00)00418-4keywords:
subject
Has Abstractpub_date
2000-12-01 00:00:00pages
403-11issue
2eissn
0021-9150issn
1879-1484pii
S0021-9150(00)00418-4journal_volume
153pub_type
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