Lipoprotein(a) induces cell growth in rat peritoneal macrophages through inhibition of transforming growth factor-beta 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-beta (TGF-beta) dose-dependently, and also by the addition of plasmin, which converts latent TGF-beta to an active form. Moreover, the amounts of endogenous active TGF-beta 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-beta activation. The capacity of Lp(a) to stimulate macrophage growth shown here could be novel atherogenic function of Lp(a).
Sato
Y
Y
Department of Metabolic Medicine, Kumamoto University School of Medicine, Japan.
Kobori
S
S
Sakai
M
M
Yano
T
T
Higashi
T
T
Matsumura
T
T
Morikawa
W
W
Terano
T
T
Miyazaki
A
A
Horiuchi
S
S
Shichiri
M
M
D000818:Animals; D001054:Apolipoproteins A / Q000494:pharmacology; D001161:Arteriosclerosis / Q000209:etiology*; D002455:Cell Division / Q000187:drug effects; D002478:Cells, Cultured; D004705:Endocytosis / Q000187:drug effects; D005341:Fibrinolysin / Q000494:pharmacology; D017270:Lipoprotein(a) / Q000494:pharmacology*; D008075:Lipoproteins, HDL / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D017737:Macrophages, Peritoneal / Q000187:drug effects*; D008297:Male; D010084:Oxidation-Reduction; D051381:Rats; D017208:Rats, Wistar; D016212:Transforming Growth Factor beta / Q000037:antagonists & inhibitors* / Q000097:blood / Q000494:pharmacology
D001054:Apolipoproteins A; D017270:Lipoprotein(a); D008075:Lipoproteins, HDL; D008077:Lipoproteins, LDL; D016212:Transforming Growth Factor beta; D005341:Fibrinolysin