Effects of wild-type (Trp72) and mutant (Arg72) apolipoprotein(a) kringle IV-10 on the proliferation of human arterial smooth muscle cells

【Abstract】 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 β 1 (TGF-β 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-β 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-β 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).更多还原