Effects of wild-type (Trp72) and mutant (Arg72) apolipoprotein(a) kringle IV-10 on the proliferation of human arterial smooth muscle cells.
OBJECTIVE
To assess the atherogenicity of lipoprotein(a), the effect of the heterogeneity of lysine binding of apolipoprotein(a) [apo(a)], a plasminogen-like glycoprotein component on the proliferation of human arterial smooth muscle cells (SMCs).


METHODS
Both wild type (wt) Trp72 and mutant (mut) Trp72-->Arg forms of apo(a) kringle IV-10 were expressed by employing a GST-gene fusion system into E. coli. The proliferation of SMCs was determined by flow cytometry and MTT colorimetry. Enzyme-linked immunosorbent assay (ELISA) assay was used to detect the active form of transforming growth factor beta(1) (TGF-beta(1)).


RESULTS
Apo(a) wt-kringle IV-10 that has lysine binding properties possessed a growth-stimulating activity to SMCs on a dose-dependence manner by stimulating cells in the G(1)/G(0) phase of cell cycle to S and G(2)/M phase, and reduced significantly the amounts of endogenous active TGF-beta(1) in culture when compared with the control medium and the GST group (2.4 +/- 0.5 vs 8.6 +/- 1.6 and 9.1 +/- 1.7 ng/ml, P < 0.01). The growth-stimulating effect of apo(a) mut-kringle IV-10 deficient in lysine binding was negligible.


CONCLUSIONS
Apo(a) induces SMCs growth by inhibiting the activation of latent TGF-beta(1), an activity that may involve the ability of apo(a) kringle IV-10 to bind lysine. The mitogenic effect of apo(a) wt-kringle IV-10 on SMCs might play an active role in the atherogenic function of lipoprotein(a).
Yu
Hong
H
Department of Biochemistry and Molecular Biology, School of Medicine, Wuhan University, Wuhan 430071, China. wu_yuhongcn@yahoo.com
Hong
Jialing
J
Wang
Binghua
B
Peng
Fangfang
F
Li
Xiaoming
X
He
Chunyan
C
D001053:Apolipoproteins / Q000235:genetics / Q000378:metabolism*; D053241:Apoprotein(a); D002455:Cell Division / Q000502:physiology; D006801:Humans; D066298:In Vitro Techniques; D018082:Kringles / Q000235:genetics*; D017270:Lipoprotein(a) / Q000235:genetics / Q000378:metabolism*; D009131:Muscle, Smooth, Vascular / Q000166:cytology*; D016212:Transforming Growth Factor beta / Q000378:metabolism
D001053:Apolipoproteins; D017270:Lipoprotein(a); D016212:Transforming Growth Factor beta; D053241:Apoprotein(a)