ROLE OF ACTIVIN-A AND FOLLISTATIN IN FOAM CELL-FORMATION OF THP-1 MACROPHAGES

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 functio n, 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 ce ll formation and cellular cholesteryl ester accumulation were decrease d. This downregulation was paralleled by a reduction in cell associati on and degradation of acetylated LDL. The inhibitory effect of activin -A on cell association and degradation was dose dependent, and the eff ect was blocked by concomitant addition of follistatin. Activin-A (5 n mol/L) also decreased the Bmax for acetylated LDL and scavenger recept or mRNA expression. Follistatin showed an effect opposite to that of a ctivin-A and promoted M phi foam cell formation and cellular cholester yl ester accumulation. It increased binding, cell association, and deg radation of acetylated LDL and upregulated scavenger receptor mRNA exp ression. Because follistatin is the binding protein for activin-A, fol listatin's effect is considered to be mediated by blocking the inhibit ory effect of intrinsic activin-A. These results indicate that activin -A inhibits and follistatin promotes M phi foam cell formation by regu lating 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.