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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) Trp72Arg 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).
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 The 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-dependent manner by stimulating cells in 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).