_enti_e9
_enti_e1
_enti_e3
_enti_e2
_enti_e4
_enti_e55
_enti_e53
_enti_e59
_enti_e54
_enti_e52
_enti_e56
_enti_e51
_enti_e50
_enti_e61
_enti_e57
_enti_e58
_enti_e62
_enti_e60
g1_fact_g1
g1_fact_g14
g2_fact_g12
g2_fact_g13
p1_propro_p1
PMID: 9261091
There the LDL can undergo oxidative modification catalyzed by any of the major cell types found in arterial lesions, i.e. endothelial cells, smooth muscle cells, or macrophages.
PMID: 9261091,6587396
As mentioned above, modification of LDL by endothelial cells in vitro can be completely prevented by the addition of antioxidants such as vitamin E or butylated hydroxytoluene
PMID: 9261091, 8195716,9013599
Which of these contribute to LDL oxidation in vivo and to what extent is still uncertain, but analysis of products isolated from atherosclerotic lesions strongly supports the involvement of lipoxygenases and of myeloperoxidase
PMID: 9261091,9054771
Indeed this has now been demonstrated in several different animal models (the LDL receptor-deficient rabbit, the cholesterol-fed New Zealand White rabbit, the cholesterol-fed hamster, the cholesterol-fed cynomolgus monkey, the LDL receptor-deficient mouse, and the apoprotein E-deficient mouse) and using one of several different antioxidants (probucol, butylated hydroxytoluene, diphenylphenylenediamine, and vitamin E)
c1 cso30:c:InputProcess connector
c16 cso30:c:InputInhibitor connector
c17 cso30:c:InputInhibitor connector
c18 cso30:c:InputAssociation connector
c23 cso30:c:InputInhibitor connector
c26 cso30:c:InputInhibitor connector
c2 cso30:c:OutputProcess connector
p2_propro_p2
PMID: 9261091,1695010
Even minimally oxidized LDL (MM-LDL) can increase adherence and penetration of monocytes, in part by stimulating release of MCP-1 from endothelial cells
c3 cso30:c:InputAssociation connector
c5 cso30:c:InputAssociation connector
c4 cso30:c:OutputProcess connector
p3_propro_p3
PMID: 9261091,1690354
MM-LDL can also stimulate release of MCSF, which can induce differentiation of the monocyte into a cell with the phenotypic pattern of the tissue macrophage, including an increase in expression of SRA
c7 cso30:c:InputAssociation connector
c8 cso30:c:InputAssociation connector
c6 cso30:c:OutputProcess connector
p4_propro_p4
c9 cso30:c:InputAssociation connector
c10 cso30:c:OutputProcess connector
p5_propro_p5
PMID: 9261091, 1690354
MM-LDL can also stimulate release of MCSF, which can induce differentiation of the monocyte into a cell with the phenotypic pattern of the tissue macrophage, including an increase in expression of SRA
PMID: 9261091
More fully oxidized LDL (OxLDL) is itself directly chemotactic for monocytes, and it is also, of course, one of the major ligands for SRA and other receptors on the arterial macrophage that contribute to foam cell formation.
c11 cso30:c:InputAssociation connector
c12 cso30:c:OutputProcess connector
p6_propro_p6
PMID: 9261091
More fully oxidized LDL (OxLDL) is itself directly chemotactic for monocytes, and it is also, of course, one of the major ligands for SRA and other receptors on the arterial macrophage that contribute to foam cell formation.
PMID: 9261091,6301324
As already mentioned, the first property of oxidized LDL to be discovered that makes it more atherogenic than native LDL is that it is recognized by the scavenger receptors and can therefore give rise to foam cells
c13 cso30:c:InputProcess connector
c14 cso30:c:InputProcess connector
c15 cso30:c:OutputProcess connector
p1_propro_p7
PMID: 9261091
There the LDL can undergo oxidative modification catalyzed by any of the major cell types found in arterial lesions, i.e. endothelial cells, smooth muscle cells, or macrophages.
PMID: 9261091,6587396
As mentioned above, modification of LDL by endothelial cells in vitro can be completely prevented by the addition of antioxidants such as vitamin E or butylated hydroxytoluene
PMID: 9261091,8195716,9013599
Which of these contribute to LDL oxidation in vivo and to what extent is still uncertain, but analysis of products isolated from atherosclerotic lesions strongly supports the involvement of lipoxygenases and of myeloperoxidase
PMID: 9261091,9054771
Indeed this has now been demonstrated in several different animal models (the LDL receptor-deficient rabbit, the cholesterol-fed New Zealand White rabbit, the cholesterol-fed hamster, the cholesterol-fed cynomolgus monkey, the LDL receptor-deficient mouse, and the apoprotein E-deficient mouse) and using one of several different antioxidants (probucol, butylated hydroxytoluene, diphenylphenylenediamine, and vitamin E)
c19 cso30:c:InputProcess connector
c20 cso30:c:InputAssociation connector
c21 cso30:c:InputInhibitor connector
c22 cso30:c:InputInhibitor connector
c24 cso30:c:InputInhibitor connector
c25 cso30:c:InputInhibitor connector
c45 cso30:c:OutputProcess connector
p8_propro_p8
PMID: 9261091,1858568
In fact the first antioxidant tested, probucol, does indeed have additional biological properties that might be relevant , including the ability to inhibit interleukin-1 release and to increase expression of cholesterol ester transfer protein.
c27 cso30:c:InputAssociation connector
c29 cso30:c:InputInhibitor connector
c28 cso30:c:OutputProcess connector
p9_propro_p9
PMID: 9261091,1858568
In fact the first antioxidant tested, probucol, does indeed have additional biological properties that might be relevant , including the ability to inhibit interleukin-1 release and to increase expression of cholesterol ester transfer protein.
c30 cso30:c:InputAssociation connector
c31 cso30:c:OutputProcess connector
p10_propro_p10
PMID: 9261091,7685021,7520436
The B class of scavenger receptors includes CD36 and SR-B1
c32 cso30:c:InputProcess connector
c33 cso30:c:InputProcess connector
c34 cso30:c:OutputProcess connector
p10_propro_p11
PMID: 9261091,7685021,7520436
The B class of scavenger receptors includes CD36 and SR-B1
c35 cso30:c:InputProcess connector
c36 cso30:c:InputProcess connector
c37 cso30:c:OutputProcess connector
p12_propro_p12
PMID: 9261091,7568176,8962141
Recent studies have shown that macrosialin and its human homologue, CD68, can bind OxLDL in ligand blots and that antibodies against CD68 can partially inhibit the binding and uptake of OxLDL by a human monocyte-derived cell line, the THP-1 cell line
c38 cso30:c:InputProcess connector
c39 cso30:c:InputProcess connector
c40 cso30:c:OutputProcess connector
p13_propro_p13
PMID: 9261091,8385467
The role of CD36 in this respect has been extensively studied (63) and appears to involve cooperative interaction with alpha Vbeta 3 and thrombospondin.
c42 cso30:c:InputProcess connector
c41 cso30:c:InputProcess connector
c43 cso30:c:InputProcess connector
c44 cso30:c:OutputProcess connector
LDL_enti_MO000000290
LDL
LDL{oxidized)_enti_e5
LDL{oxidized)
MCP-1_enti_MO000017280
MCP-1
MCP1_enti_G010815
MCP1
M-CSF_enti_MO000000100
M-CSF
MCSF_enti_e6
MCSF
SRA_enti_e11
SRA
SRA_enti_e12
SRA
LDL{oxidized}:SRA_enti_e13
LDL{oxidized}:SRA
Vitamin E_enti_e14
Vitamin E
Butylated Hydroxytoulene_enti_e15
Butylated Hydroxytoulene
myeloperoxidase_enti_MO000068861
myeloperoxidase
lipoxygenase_enti_MO000021434
lipoxygenase
Probucol_enti_e16
Probucol
diphenylphenylenediamine_enti_e17
diphenylphenylenediamine
IL-1_enti_MO000000214
IL-1
IL-1_enti_e7
IL-1
Cholestrol ester transfer protein mRNA_enti_e8
Cholestrol ester transfer protein mRNA
CD36_enti_e10
CD36
CD36:LDL{oxidized}_enti_e18
CD36:LDL{oxidized}
SR-B1_enti_e19
SR-B1
SR-B1:LDL{oxidized}_enti_e20
SR-B1:LDL{oxidized}
CD68_enti_e21
CD68
Cd68:LDL{oxidized}_enti_e22
Cd68:LDL{oxidized}
Thrombospondin_enti_e23
Thrombospondin
Alpha V Beta 3_enti_e25
Alpha V Beta 3
Cd36:Alpha V Beta 3:Thrombospondin_enti_e24
Cd36:Alpha V Beta 3:Thrombospondin