Adhesion Molecules and Oxidized Low-density Lipoprotein - Adhesion Molecules - page 401

Table 2 Possible factors influencing the vascular endothelial adhesion molecule expression
induced by oxidized low-density lipoprotein
1. LDL oxidation process
Chemicals—copper ion, iron ion, lipoxygenase, phospholipase A2
Cells—endothelial cells, smooth muscle cells, monocytes, macrophages, i broblasts
Tissues—atherosclerotic tissues, xanthoma tissues
2. Responsible molecules of Ox-LDL
Lysophosphatidylcholine, PAPC, fatty acids
3. Organ specii city of endothelial cells
Aorta, coronary artery, iliac artery, umbilical vein, glomerulus, dermal microvessels
h e mechanisms of adhesion molecule expression vary depending on the oxidation process of LDL, responsible
molecules of oxidized LDL, and the organ specii city of the endothelial cells. LDL, low-density lipoprotein. Ox-LDL,
oxidized low-density lipoprotein. PAPC, 1-palmitoyl-2-arachidonoyl- sn -glycero-3-phosphorylcholine.
umbilical vein endothelial cell (HUVEC)-oxidized LDL and Cu-LDL made by
incubation of LDL with 10 μM Cu 2+ induce P-selectin, but not E-selectin, on
HUVECs (Gebuhrer et al . 1995). LDL oxidized with 5 μM Cu 2+ signii cantly
induces E-selectin expression in HUVECs (Cominacini et al . 1997b). LDL
oxidized with 1 μM Cu 2+ and MM-LDL do not change E-selectin expression
in HUVECs (Cominacini et al . 1997a). Oxidized lipoprotein (a) induces more
P-selectin protein and mRNA expression than Ox-LDL in HUVECs (Zhao and Xu
2000). h e treatment of human aortic endothelial cells (HAECs) with MM-LDL
causes an increase in intracellular P-selectin protein that is associated with MM-
LDL-induced cyclic adenosine monophosphate elevation (Vora et al . 1997). MM-
LDL therefore causes little change in P-selectin cell surface expression. However,
highly oxidized Ox-LDL, especially the oxidized fatty acids, has been shown
to induce the surface expression of P-selectin (Vora et al . 1997). h e ef ect of
lysophosphatidylcholine on E-selectin expression is negligible in HAECs, human
iliac artery endothelial cells, and HUVECs (Kume et al . 1992).
X-LDL upregulates E-selectin expression on human dermal microvascular
endothelial cells (HDMECs; Matsumoto et al . 2003). h e X-LDL-induced
expression of E-selectin on HDMECs is mediated by the tyrosine kinase-related
pathway, but not by the inhibitory G (G i )-protein or protein kinase C (PKC)
pathways (Matsumoto et al . 2003). Cu-LDL also induces E-selectin expression
on HDMECs, and this expression is incompletely inhibited by pretreatment
with pertussis toxin, a G i -protein inhibitor (Matsumoto et al . 2003). h is i nding
indicates that E-selectin expression might be mediated not only by the G i -protein
pathway but also by other pathways (except the tyrosine kinase-related pathway
and the PKC pathway).
Immunoglobulin Superfamily
In HCAECs, Cu-LDL treatment upregulates the expression of ICAM-1 and
VCAM-1 via LOX-1 (Li et al . 2002). In HUVECs, 5 μM Cu 2+ -oxidized LDL