title: Lipoprotein(a) enhances the expression of intercellular adhesion molecule-1 in cultured human umbilical vein endothelial cells.
abstract: BACKGROUND
  We reported an increase in serum lipoprotein(a) [Lp(a)] levels in patients with thromboangiitis obliterans, suggesting that Lp(a) could also contribute to the pathogenesis of cardiovascular diseases by a mechanism different from atherosclerosis. Adhesion molecules were shown to contribute to the development of not only atherosclerotic but also inflammatory vascular diseases.
  
  
  RESULTS
  We evaluated the effect of Lp(a) on the expression of intercellular adhesion molecule (ICAM)-1, vascular cell adhesion molecule (VCAM)-1, and E-selectin in human umbilical vein endothelial cells by a cell ELISA. Lp(a) dramatically enhanced the levels of ICAM-1 in a dose-dependent manner. A discernible increase in ICAM-1 expression was observed at a physiological concentration of 0.26 mmol cholesterol/L Lp(a) after 48-hour incubation. A 1.8-fold increase in ICAM-1 expression was observed 48 hours after the addition of Lp(a) (1.04 mmol cholesterol/L). Northern blot analysis demonstrated that the amount of ICAM-1 mRNA was increased after treatment with Lp(a). In contrast to ICAM-1, the expression of VCAM-1 and E-selectin was not significantly affected by Lp(a). Lp(a-) [apolipoprotein(a)- removed Lp(a) by reduction with dithiothreitol] and LDL had no significant effect on the expression of ICAM-1. In contrast, recombinant apolipoprotein(a) protein alone significantly enhanced ICAM-1 expression. Lp(a) decreased the level of active transforming growth factor (TGF)-beta in the conditioned medium. Furthermore, recombinant TGF-beta significantly decreased the Lp(a)-induced ICAM-1 expression. These findings suggested that Lp(a) may enhance the ICAM-1 expression by decreasing active TGF-beta level.
  
  
  CONCLUSIONS
  Lp(a) could contribute to the development of cardiovascular diseases by enhancing the expression of ICAM-1 in endothelial cells.
authors.affiliation: Second Department of Internal Medicine, Osaka University Medical School, Suita, Japan.
authors.forename: S
authors.initials: S
authors.lastname: Takami
authors.forename: S
authors.initials: S
authors.lastname: Yamashita
authors.forename: S
authors.initials: S
authors.lastname: Kihara
authors.forename: M
authors.initials: M
authors.lastname: Ishigami
authors.forename: K
authors.initials: K
authors.lastname: Takemura
authors.forename: N
authors.initials: N
authors.lastname: Kume
authors.forename: T
authors.initials: T
authors.lastname: Kita
authors.forename: Y
authors.initials: Y
authors.lastname: Matsuzawa
mesh_terms: D000906:Antibodies / Q000276:immunology / Q000494:pharmacology; D001054:Apolipoproteins A / Q000494:pharmacology; D015152:Blotting, Northern; D002460:Cell Line; D017077:Culture Media, Conditioned / Q000737:chemistry / Q000378:metabolism; D019040:E-Selectin / Q000187:drug effects / Q000235:genetics; D004730:Endothelium, Vascular / Q000166:cytology / Q000187:drug effects* / Q000378:metabolism; D015870:Gene Expression / Q000187:drug effects / Q000235:genetics; D005786:Gene Expression Regulation / Q000187:drug effects / Q000235:genetics; D006801:Humans; D018799:Intercellular Adhesion Molecule-1 / Q000187:drug effects* / Q000235:genetics*; D017270:Lipoprotein(a) / Q000494:pharmacology*; D008074:Lipoproteins / Q000494:pharmacology; D008077:Lipoproteins, LDL / Q000494:pharmacology; D009500:Neutralization Tests; D012333:RNA, Messenger / Q000032:analysis / Q000378:metabolism; D011994:Recombinant Proteins / Q000494:pharmacology; D016212:Transforming Growth Factor beta / Q000187:drug effects / Q000276:immunology / Q000378:metabolism; D014409:Tumor Necrosis Factor-alpha / Q000494:pharmacology; D014471:Umbilical Veins / Q000166:cytology; D015854:Up-Regulation / Q000276:immunology
chemical_list: D000906:Antibodies; D001054:Apolipoproteins A; D017077:Culture Media, Conditioned; D019040:E-Selectin; D017270:Lipoprotein(a); D008074:Lipoproteins; D008077:Lipoproteins, LDL; D012333:RNA, Messenger; D011994:Recombinant Proteins; D016212:Transforming Growth Factor beta; D014409:Tumor Necrosis Factor-alpha; D018799:Intercellular Adhesion Molecule-1