Background Elevated levels of lipoprotein(a) [Lp(a)] are associated wi
th premature atherosclerosis; however, the mechanisms are not known. R
ecruitment of monocytes to the blood vessel wall is an early event in
atherogenesis. Methods and Results This study has found that unoxidize
d Lp(a) induced human umbilical vein endothelial cells (HUVECs) to sec
rete monocyte chemotactic activity (MCA), whereas LDL under the same c
onditions did not. In the absence of HUVECs, Lp(a) had no direct MCA.
Endotoxin was shown not to be responsible for the induction of MCA. Ac
tinomycin D and cycloheximide inhibited the HUVEC response to Lp(a), i
ndicating that protein and RNA synthesis were required. The apolipopro
tein(a) [apo(a)] portion of Lp(a) was identified as the structural com
ponent of Lp(a) responsible for inducing MCA. Lp(a) and apo(a) also st
imulated human coronary artery endothelial cells to produce MCA. Granu
locyte-monocyte colony-stimulating factor (GM-CSF) antigen was not det
ected in the Lp(a)-conditioned medium, nor was monocyte chemoattractan
t protein-1 mRNA induced in HUVECs by Lp(a). Conclusions These finding
s suggest that Lp(a) may be involved in the recruitment of monocytes t
o the vessel wall and provide a novel mechanism for the participation
of Lp(a) in the atherogenic process.