Biomedical Engineering Reference
In-Depth Information
X-LDL induces monocyte adhesion to HDMECs through VCAM-1 and
E-selectin, but not ICAM-1 (Matsumoto
et al
. 2003). Cu-LDL upregulates monocyte
adhesion to HDMECs via ICAM-1, VCAM-1 and E-selectin (Matsumoto
et al
.
2003). Ox-LDL increases monocyte adhesion to EA.hy 926, an endothelial cell
line, independently of ICAM-1, VCAM-1, and nuclear factor-kappaB (NF-κB)
activation (Dwivedi
et al
. 2001). Chimeric sCD36-Ig protein blocked the Ox-
LDL-induced adhesion of monocytes to endothelial cells through ICAM-1, thus
indicating that this chimeric protein can ef ectively compete for the binding of Ox-
LDL to membrane-expressed CD36 (Stewart and Nagarajan 2006). h e toll-like
receptor (TLR) 4/NF-κB signaling pathway plays a role in monocyte-endothelial
adhesion induced by Ox-LDL (Yang
et al
. 2005). Anti-human TLR4 monoclonal
antibody or transinfection with a functional mutant of TLR4 remarkably inhibit
NF-κB activity and signii cantly reduce the degree of monocyte-endothelial
adhesion, but anti-human TLR2 monoclonal antibody does not have a similar
ef ect (Yang
et al
. 2005).
LDL oxidation can induce adhesion molecule expression on vascular endothelial
cells and subsequent monocyte adhesion to the endothelial cells. h ese mechanisms
are regulated by various intracellular signaling pathways in the cell membranes. A
variety of drugs and nutrients have been used to regulate the adhesion molecule
expression and the degree of monocyte adhesion, and the mechanisms of these
substances have been elucidated by recent studies
(Table 3)
. Further investigations
that clarify the mechanisms of adhesion molecule expression will result in more
specii c and ef ective treatment modalities for atherosclerosis and cutaneous
xanthomas.
Table 3
Key points of therapeutic targets of the molecules involved in the adhesion
molecule expression induced by oxidized low-density lipoprotein
Drug
Molecules
Adhesion molecules
References
Simvastatin
NF-κB
E-selectin, P-selectin,
Li
et al
. 2002
ICAM-1, VCAM-1
Atorvastatin
NF-κB
E-selectin, P-selectin,
Li
et al
. 2002
ICAM-1, VCAM-1
SH-containing
NF-κB, ROS
E-selectin, ICAM-1,
Cominacini
et al
. 2002,
angiotensin converting
VCAM-1
Liu
et al
. 2002
enzyme inhibitor
Docosahexaenoic acid
PKB
P-selectin, ICAM-1
Chen
et al
. 2003
Eicosapentaenoic acid
PKB
P-selectin, ICAM-1
Chen
et al
. 2003
Diallyl disuli de
PKA, PKB
E-selectin, VCAM-1
Lei
et al
. 2008
Diallyl trisuli de
PKA, PKB
E-selectin, VCAM-1
Lei
et al
. 2008
Butyrate
NF-κB
ICAM-1, VCAM-1
Siennicka 2005
Propionate
NF-κB
ICAM-1, VCAM-1
Siennicka 2005
A variety of drugs and nutrients have been used to regulate the adhesion molecule expression, and
the mechanisms of these substances have all been elucidated by recent studies. NF-κB, nuclear factor-
kappaB. ROS, reactive oxygen species. PKA, protein kinase A. PKB, protein kinase B. ICAM-1,
intercellular adhesion molecule 1. VCAM-1, vascular cell adhesion molecule 1.
