Carbamylated Low-density Lipoprotein and Adhesion Molecules - Adhesion Molecules - page 381

with other modii ed LDLs (Chen et al. 2005, Inoue et al. 2005). h erefore, it seems
plausible that cLDL-induced monocyte adhesion is mediated through scavenger
receptors and subsequent ICAM-1/VCAM-1 overexpression.
Acceleration of Monocyte Adhesion to Endothelial Cells by
cLDL
Our recent study showed that cLDL induces monocyte adhesion by endothelial
cells in vitro (Apostolov et al. 2007b). To determine whether cLDL causes monocyte
adhesion to endothelial cells, cLDL (200 μg/mL) was applied to endothelial cells
for varying periods of time and l uorescently labeled U937 cells were allowed
to adhere for 30 min. We found a signii cant increase of monocyte adhesion to
the endothelial cells treated for 12 hr or longer with cLDL, while nLDL and the
vehicle control did not cause any monocyte adhesion (Fig. 3) . OxLDL that was
previously described to induce monocyte adhesion (Li and Mehta 2000) was used
as a positive control. A 6 hr or longer treatment with oxLDL (200 μg/mL) caused
a four-fold increase of monocyte adhesion to the endothelial cells. It is interesting
that once monocyte adhesion to oxLDL-treated endothelial cells reached the
maximum, no further increase of adhesion was observed. As opposed to oxLDL,
cLDL caused signii cant monocyte adhesion versus nLDL and vehicle control only
at er a 12 hr course, followed then by a further increase of monocyte adhesion over
the level of oxLDL. At the end of the 24 hr course, the adhesion induced by cLDL
was higher than that induced by oxLDL. In another experiment, freshly isolated
human monocytes also had higher rate of adherence to endothelial cells pretreated
with both cLDL and oxLDL (Fig. 4) . cLDL- or oxLDL-activated endothelial cells
also attracted monocytes under l ow conditions, in laminar l ow chambers. h ese
results demonstrate that HCAECs treated with modii ed LDLs attracted more
U937 cells or freshly isolated monocytes than vehicle- or nLDL-treated cells both
in static adhesion experiments and in l ow chambers.
cLDL Induces ICAM-1 and VCAM-1 Expression in Vascular
Endothelial and Smooth Muscle Cells
h e expression of adhesion molecules, ICAM-1, VCAM-1 and P-selectin, and a
chemokine, MCP-1, which could potentially mediate cLDL-induced monocyte
adhesion to endothelial cells, was recently studied (Apostolov et al. 2007b).
HCAECs were treated with cLDL or nLDL for 24 hr, and the expressions of
adhesion molecules were determined using cell ELISA. In this approach, the
expression of MCP-1 and P-selectin was not induced by the treatment with cLDL
in comparison to nLDL. However, the expression of ICAM-1 and VCAM-1
was signii cantly increased by cLDL. ICAM-1 was induced to a higher degree
than VCAM-1. Contrary to cLDL, oxLDL did not af ect ICAM-1 and VCAM-1