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(Arteriosclerosis, Thrombosis, and Vascular Biology. 1997;17:2389-2394.)
© 1997 American Heart Association, Inc.

Articles

Role of Activin-A and Follistatin in Foam Cell Formation of THP-1 Macrophages

Koichi Kozaki; Masahiro Akishita; Masato Eto; Masao Yoshizumi; Kenji Toba; Satoshi Inoue; Michiro Ishikawa; Masayoshi Hashimoto; Tatsuhiko Kodama; Nobuhiro Yamada; Hajime Orimo; ; Yasuyoshi Ouchi

From the Department of Geriatrics (K.K., M.A., M.E., M.Y., K.T., S.I., M.I., M.H., H.O., Y.O.) and the Third Department of Internal Medicine (N.Y.), Faculty of Medicine, and the Department of Molecular Biology and Medicine, Research Center for Advanced Science and Technology (T.K.), University of Tokyo, Tokyo, Japan.

Correspondence to Yasuyoshi Ouchi, MD, Department of Geriatrics, Faculty of Medicine, University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113, Japan.

Abstract Macrophage (M) foam cell formation is a characteristic event that occurs in the early stage of atherosclerosis. To examine the roles of activin-A, a member of the transforming growth factor-ß superfamily, and follistatin, the binding protein for activin-A, in M function, we investigated their effects on foam cell formation of THP-1 Ms. When THP-1 Ms were treated with activin-A (5 nmol/L), foam cell formation and cellular cholesteryl ester accumulation were decreased. This downregulation was paralleled by a reduction in cell association and degradation of acetylated LDL. The inhibitory effect of activin-A on cell association and degradation was dose dependent, and the effect was blocked by concomitant addition of follistatin. Activin-A (5 nmol/L) also decreased the Bmax for acetylated LDL and scavenger receptor mRNA expression. Follistatin showed an effect opposite to that of activin-A and promoted M foam cell formation and cellular cholesteryl ester accumulation. It increased binding, cell association, and degradation of acetylated LDL and upregulated scavenger receptor mRNA expression. Because follistatin is the binding protein for activin-A, follistatin's effect is considered to be mediated by blocking the inhibitory effect of intrinsic activin-A. These results indicate that activin-A inhibits and follistatin promotes M foam cell formation by regulating scavenger receptor mRNA expression. We conclude that activin-A and follistatin play important roles in the process of atherosclerosis by regulating M foam cell formation.

Key Words: activin-A • follistatin • scavenger receptor • foam cell formation

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