Biomedical Engineering Reference
In-Depth Information
Oxidation by Cells and Tissues
LDL is oxidized
in vitro
by incubation with endothelial cells, smooth muscle cells,
monocytes, macrophages, and i broblasts. LDL oxidation is mediated by superoxide
anions generated from monocytes and smooth muscle cells and by lipoxygenase
from endothelial cells and macrophages. However, the precise mechanism of
LDL oxidation is still controversial. Transition metals, such as Fe
2+
and Cu
2+
, are
required for LDL oxidation by cells. h erefore,
in vitro
LDL oxidation experiments
have usually been performed in Fe
2+
-containing medium.
h ere are as yet only a few reports on LDL oxidation using tissue specimens.
Gruel samples of human atherosclerotic lesions are capable of oxidizing LDL in
the presence of transition metal ions. Ox-LDL is produced by incubation with
the extracts from atherosclerotic plaques using centrifugation. Xanthoma lesion-
oxidized LDL (X-LDL) is obtained by incubating human LDL with experimental
rabbit xanthoma tissues in RPMI-1640 medium without Cu
2+
and Fe
2+
. h e
experimental xanthoma lesions are induced by intradermal injections of dextran
sulfate solution at dorsal sites of rabbits fed a high cholesterol diet. h e lipid
compositions of the experimental rabbit xanthoma lesions are similar to those
observed in human xanthoma lesions.
RECEPTORS THAT CAN BIND Ox-LDL
Ox-LDL binds to a diverse range of transmembrane proteins that are collectively
termed scavenger receptors. h ese receptors are also capable of binding a wide
variety of lipid- and lipoprotein-based ligands.
Scavenger Receptors
h e scavenger receptor family can be broadly classii ed into eight subclasses (A-H)
that bear little sequence homology to each other, but they do recognize common
ligands. At least seven scavenger receptors have been detected in human vascular
endothelial cells—scavenger receptor with C-type lectin (SRCL), scavenger
receptor BI (SR-BI), CD36, lectin-like oxidized LDL receptor-1 (LOX-1),
scavenger receptor expressed on endothelial cell-I (SREC-I), scavenger receptor for
phosphatidylserine and oxidized lipoprotein (SR-PSOX), and fasciclin, epidermal
growth factor (EGF)-like, laminin-type EGF-like and link domain-containing
Other Receptors
Alternative receptors that bind Ox-LDL are described in this section. One of the
earliest consequences of LDL oxidation is LDL aggregation, and the aggregated
