Involvement of interleukin-6 in atherosclerosis but not in the prevention of fatty streak formation by 17β-estradiol in apolipoprotein E-deficient mice
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Abstract
Interleukin-6 (IL-6) gene expressed in bone marrow-derived stromal cells and osteoblasts
contributes to the state of mineralization and its control by estradiol may be involved
in the development of post-menopausal osteoporosis. Since IL-6 is also expressed in
the different cell populations of the arterial wall, the purpose of this study was
to gain more insight into its involvement in the atherosclerotic process and the atheroprotective
effect of estradiol by studying double deficient mice at the apolipoprotein E and
IL-6 loci (IL-6(-/-)/E(-/-)). At 1 year of age, IL-6(-/-)/E(-/-) mice showed similar
hypercholesterolemia to IL-6(+/+)/E(-/-) mice but presented significantly larger and
more calcified lesions. In younger mice (sixteen weeks of age), no significant difference
in fatty streaks could be detected in IL-6(+/+)/E(-/-), IL-6(+/-)/E(-/-) and IL-6(-/-)/E(-/-)
mice on a normal chow diet. Estrogen supplementation at this age induced a decrease
of fatty streak formation in all three genotypes. The combined data indicate that
IL-6 expression is involved at the fibrous plaque stage of the atherosclerotic process
but does not constitute a direct target for estradiol to prevent fatty streak formation.