Lipoprotein(a) induces cell growth in rat peritoneal macrophages through inhibition of transforming growth factor-β activation

To elucidate the atherogenicity of lipoprotein(a) (Lp(a)), we examined its growth-stimulating activity in rat resident peritoneal macrophages. When macrophages were incubated with Lp(a), cell numbers were increased 1.5-fold as compared with control macrophages. Furthermore, apolipoprotein(a) (apo(a)), a plasminogen-like glycoprotein which is covalently attached to a low density lipoprotein-like particle (Lp(a-)), also induced macrophage growth, while the growth-stimulating effect of Lp(a-) was negligible. These results suggest that apo(a) plays an active role in the mitogenic activity of Lp(a). Lp(a)-induced macrophage growth was inhibited by exogenously added active transforming growth factor-β (TGF-β) dose-dependently, and also by the addition of plasmin, which converts latent TGF-β to an active form. Moreover, the amounts of endogenous active TGF-β in the medium were significantly reduced by the incubation with Lp(a). It is evident from these results that Lp(a) induces macrophage growth by inhibiting TGF-β activation. The capacity of Lp(a) to stimulate macrophage growth shown here could be a novel atherogenic function of Lp(a).