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).
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).
Authors: Jenny Sandmark; Anna Tigerström; Tomas Akerud; Magnus Althage; Thomas Antonsson; Stefan Blaho; Cristian Bodin; Jonas Boström; Yantao Chen; Anders Dahlén; Per-Olof Eriksson; Emma Evertsson; Tomas Fex; Ola Fjellström; David Gustafsson; Margareta Herslöf; Ryan Hicks; Emelie Jarkvist; Carina Johansson; Inge Kalies; Birgitta Karlsson Svalstedt; Fredrik Kartberg; Anne Legnehed; Sofia Martinsson; Andreas Moberg; Marianne Ridderström; Birgitta Rosengren; Alan Sabirsh; Anders Thelin; Johanna Vinblad; Annika U Wellner; Bingze Xu; Ann-Margret Östlund-Lindqvist; Wolfgang Knecht Journal: J Biol Chem Date: 2020-03-04 Impact factor: 5.157
Authors: Kirsten Riches; Larissa Franklin; Azhar Maqbool; Michelle Peckham; Matthew Adams; Jacquelyn Bond; Philip Warburton; Nicole T Feric; Marlys L Koschinsky; David J O'Regan; Stephen G Ball; Neil A Turner; Karen E Porter Journal: Int J Biochem Cell Biol Date: 2013-05-31 Impact factor: 5.085