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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:1691-1700.)
© 1997 American Heart Association, Inc.

Articles

Effect of 17ß-Estradiol on Metabolism of Acetylated Low-Density Lipoprotein by THP-1 Macrophages in Culture

Sulistiyani R.W. St Clair

From the Department of Pathology, The Bowman Gray School of Medicine of Wake Forest University, Winston-Salem, NC.

Correspondence to Richard W. St Clair, PhD, The Bowman Gray School of Medicine of Wake Forest University, Department of Pathology, Medical Center Blvd, Winston-Salem, NC 27157-1072.

Abstract Evidence from numerous epidemiological and animal studies has shown a protective effect of estrogens on the development of atherosclerosis. Since not all of the beneficial effects of estrogen can be explained by alterations in plasma lipoprotein profiles, estrogens may have a direct effect on the arterial wall on one or more of the key steps in the pathogenesis of atherosclerosis. In the present study we tested the hypothesis that estrogens decrease macrophage foam cell formation by reducing lipoprotein uptake via the scavenger receptor pathway. Incubation of the human THP-1 macrophage cell line with 17ß-estradiol reduced the uptake and metabolism of ¹²⁵I-labeled human acetylated LDL (acLDL) in a concentration-dependent manner (from 10^-9 to 10^-5 mol/L) by 30% to 40% at the highest concentrations used. This decrease was accompanied by a reduction in cholesterol accumulation and esterification. When chloroquine was used to block lysosomal degradation, 17ß-estradiol retained its ability to decrease accumulation of acLDL. This finding suggested that the effect of estrogen occurs before degradation of acLDL by lysosomes. 17ß-Estradiol had no effect on binding of ¹²⁵I-acLDL at 4°C. When ¹²⁵I-acLDL was bound at 4°C and warmed to 37°C, less acLDL was internalized and degraded in cells treated with 17ß-estradiol, due to greater dissociation of the bound acLDL from the surface of estrogen-treated cells during internalization. We conclude that as a result of the estrogen-induced increase in dissociation of acLDL, less lipoprotein cholesterol is delivered to macrophages, resulting in a reduced rate of foam cell formation. This may be one mechanism by which estrogens reduce the development of atherosclerosis.

Key Words: estrogen • acLDL metabolism • macrophage scavenger receptor • foam cells • atherosclerosis

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