Role of activin-A and follistatin in foam cell formation of THP-1 macrophages.

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Macrophage (M phi) 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-beta superfamily, and follistatin, the binding protein for activin-A, in M phi function, we investigated their effects on foam cell formation of THP-1 M phi s. When THP-1 M phi s 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 phi 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 phi 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 phi foam cell formation.