From the Second Department of Internal Medicine, Osaka University Medical
School, Suita, Osaka, and the Department of Geriatric Medicine, Graduate
School of Medicine, Kyoto University Medical School, Kyoto, Japan.
Correspondence to Shizuya Yamashita, MD, PhD, Second Department of Internal Medicine, Osaka University Medical School, 2–2, Yamadaoka, Suita, Osaka 565, Japan. E-mail shizu{at}imed2.med.osaka-u.ac.jp
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.
Methods and 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)-ß in the conditioned medium.
Furthermore, recombinant TGF-ß 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-ß
level.
Conclusions—Lp(a) could contribute to the development of
cardiovascular diseases by enhancing the expression of
ICAM-1 in endothelial cells.
© 1998 American Heart Association, Inc.
Clinical Investigation and Reports
Lipoprotein(a) Enhances the Expression of Intercellular Adhesion Molecule-1 in Cultured Human Umbilical Vein Endothelial Cells
Key Words: cardiovascular diseases • cells • growth substances • leukocytes • lipoproteins
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