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J Biol Chem, Vol. 274, Issue 37, 25959-25962, September 10, 1999
,From the Department of Cell Biology, Lerner Research Institute, Cleveland Clinic Foundation, Cleveland, Ohio 44195
The oxidation of lipoproteins has been proposed
as a biological process that initiates and accelerates arterial lesion
development (1-5). Oxidized lipoproteins accumulate in lesions (6) and may form at other inflammatory sites. Whether the oxidized lipoprotein is an initiator or accelerator of disease is the subject of
speculation, debate, and intensive study. Various cellular and
biochemical mediators of lipoprotein oxidation in vivo have
been proposed, but none has yet been proven to be responsible.
Two decades ago we demonstrated that low density lipoprotein
(LDL),1 the plasma level of
which correlates with the risk of atherosclerosis, could injure
endothelial cells (ECs) in culture (7). The capacity of LDL to injure
cells was directly related to the level of LDL oxidation, and we
speculated on a possible role for oxidized LDL-mediated endothelial
injury in atherogenesis (8, 9). Contemporaneously, Dr. Daniel
Steinberg's group (10, 11) demonstrated that LDL exposed to cultured
ECs was altered such that it became a ligand for scavenger receptors.
In 1984, both Steinberg's group and ours (12, 13) demonstrated that
the "EC-modified LDL" they had characterized and the "oxidized
LDL" we had described were the same entity. Their report highlighted
the macrophage recognition of the EC-oxidized lipoprotein, and ours the
capacity of EC or smooth muscle cell (SMC)-oxidized LDL to injure
cells. These papers introduced the concept that reactive oxygen species
from vascular cells could transform LDL, causing it to exhibit
dramatically altered composition and atherogenic properties. The first
demonstration that certain leukocyte populations could oxidize LDL
employed human neutrophils and activated populations of adherent human monocytes, cells well known to generate abundant reactive oxygen species in vitro and in vivo (14).
The identity of the cells responsible for the oxidation of LDL
that accumulates in lesions is uncertain. Although it is well known
that free ferrous or cupric ions catalyze lipid peroxidation reactions
in vitro, the presence of free metal ions in vivo
is doubted (15). Multiple mechanisms exist in vivo for
binding free transition metal ions, rendering them redox-inactive
(15-17). In this minireview, we take the position that
monocyte-derived macrophages are likely candidates to mediate the
in vivo oxidation of lipoproteins, because they are
prominent in arterial lesions, known to generate
activation-dependent reactive oxygen species, and, unlike
EC and SMC (12, 18), capable in vitro of LDL oxidation in
media free of metal ion additives. In vitro LDL appears to be oxidized extracellularly without interaction with the LDL receptor (19-21). There are multiple potential pathways through which
monocytes-macrophages may promote extracellular LDL oxidation. In this
review we evaluate cellular mechanisms (both enzymatic and
non-enzymatic) for LDL oxidation. We use the term
"monocyte-macrophage" as a shorthand reference to in
vitro studies performed on isolated monocytes, macrophages, and
monocyte-like cell lines.
The presence of free copper or iron ions in vivo is
unlikely, but an interesting concept in redox
metal-dependent oxidation of LDL by phagocytes was recently
introduced. The idea followed the surprising observation that the
copper-containing acute phase plasma protein, ceruloplasmin (Cp),
studied for years as an antioxidant, could act instead as a potent
oxidant of LDL (22). The oxidant capacity of Cp may have been
overlooked previously because of the difficulty in preserving Cp in an
undegraded state during its purification (23). Cp is a 132-kDa
glycoprotein that contains seven copper atoms per molecule and carries
most of the copper in blood. We found that LDL exposed to Cp exhibited
many characteristics of LDL oxidized in the presence of free cupric ion
(22). This oxidant activity of Cp in vitro has been verified
by other laboratories (24-26).
To determine whether Cp could substitute as a "physiological"
source of redox-active metal, the equivalent of normal (unevoked) plasma levels of Cp was added to cultures in which ECs or SMCs were
exposed to LDL in RPMI 1640, a cell culture medium without transition
metal ion additives. Cp markedly enhanced LDL oxidation by both cell
types (27). Proteolytic cleavage of Cp or removal of the one of its
seven copper atoms that is near His426, prevented its oxidative
action (27-29). Cell-derived superoxide anion (O Because monocytes-macrophages express Cp mRNA and protein (30, 31),
the hypothesis that cell-derived Cp contributes to LDL oxidation by
these cells was tested. A model system similar to that of Cathcart
et al. (20, 32) was adopted, which used the human
myelomonocytic cell line, U937, activated by zymosan in RPMI 1640 medium. Exogenous Cp added to unactivated U937 cells caused LDL
oxidation to an extent similar to that by zymosan in the absence of
exogenous Cp (33). Zymosan induced Cp mRNA and (after a 5-6-h lag
following activation) Cp protein synthesis (33). This lag coincided
with the lag prior to measurable LDL oxidation previously reported (34,
35). A neutralizing antibody to Cp blocked LDL oxidation by activated
U937 cells, as did antisense oligodeoxyribonucleotides (ODN) targeted
against segments of the Cp mRNA (33). These studies suggested a
possible in vivo role for Cp in monocyte-macrophage-mediated
LDL oxidation, but they also revealed that cell-derived factors in
addition to Cp are required for optimal oxidation. Among the candidates
are, for example, O Factors that stimulate monocyte-macrophage Cp production and could
contribute to Cp accumulation in vivo include endotoxin (31)
and interferon (IFN)- The studies of Cp in cell-mediated LDL oxidation suggest other
protein-bound redox-active transition metals might also participate in
extracellular oxidation events. Under physiological conditions globin
degradation products such as hemin (41) and holo forms of iron binding
proteins such as transferrin (25) and ferritin (42) may catalyze
oxidation reactions. The reducing agents required for activity and the
physiological significance of these protein-bound redox metals remain uncertain.
The role of O Xing et al. (48) provided evidence that systems using
zymosan as an activator may in fact be metal ion-dependent
because the yeast cell walls, like transferrin and ferritin, can carry iron in an oxidized (Fe3+) state. Their results are
consistent with Zop-bound Fe3+ being reduced to
Fe2+ by cell-derived O The formation of O Are there other cell-derived factors required for optimal
monocyte-macrophage oxidation of LDL? Several have been studied; these
include not only Cp but also LO and MPO. LOs are non-heme iron-containing enzymes found in various cells, including
reticulocytes, monocytes-macrophages, and certain endothelial cells.
They catalyze the direct insertion of molecular oxygen into polyenoic
fatty acids, forming hydroperoxides. There are a number of ways in
which LOs could participate in LDL oxidation. LO could oxidize cellular fatty acid, cholesteryl ester, or phospholipid substrates, and the
hydroperoxide products could transfer to LDL, making LDL more susceptible to oxidation (54). If LO could come in contact with LDL, it
could use phospholipid or cholesteryl ester as substrate (55), leading
to lipid peroxidation. LO products could also participate in signal
transduction pathways regulating other monocyte-macrophage functions
involved in oxidation.
In monocyte-macrophage systems, 5-LO has been ruled out as a
participant in LDL oxidation (58, 59). Sparrow et al. (56) demonstrated that incubation of LDL with 15-LO plus phospholipase A2 led to LDL oxidation in a cell-free system; however,
15-LO alone was also shown to oxidize LDL significantly in the absence of cells (57). 15-LO inhibitors are able to block cell-mediated oxidation of LDL, but many of these inhibitors are nonspecific antioxidants, making the assertion of a role for 15-LO more difficult to demonstrate (60-62). One study reported a lack of LO involvement in
LDL oxidation by monocytes-macrophages by pointing out discrepancies between the concentrations of inhibitors required for LO inhibition and
those required to inhibit LDL oxidation (61).
Despite caveats, substantial indirect evidence links 15-LO to LDL
oxidation. In cell-free systems LO was inhibited by O Another cell-derived factor that may participate in
phagocyte-dependent oxidation of LDL is MPO. MPO is an
abundant heme protein released by activated neutrophils and monocytes
and present in some tissue macrophages such as those in vascular
lesions (65). MPO may play a role in monocyte-macrophage oxidation of
LDL by a variety of distinct pathways (66-72). MPO can act to amplify the oxidizing potential of H2O2, the
dismutation product of O Recent studies have identified another potential
MPO-dependent pathway that monocytes-macrophages may employ
for LDL oxidation that involves formation of reactive nitrogen species.
MPO can use H2O2 and nitrite
(NO2 The role of ·NO and reactive nitrogen species derived
from ·NO in LDL oxidation is an area of intense research.
·NO is a long lived free radical formed by multiple inflammatory and vascular wall cells (88). Both pro- and antioxidant effects of
·NO have been proposed. ·NO is relatively unreactive
toward most biomolecules. In cell culture systems, enhanced production
of ·NO by monocytes-macrophages exerted an antioxidant effect,
attenuating the extent of lipid peroxidation (89). However, a variety
of reactive nitrogen species derived from ·NO are capable of
oxidizing biological targets. The cellular and biochemical consequences
of ·NO and ·NO-derived reactive nitrogen species
formation on biological targets are thus complex; they have recently
been comprehensively reviewed (90-92).
The mechanisms of LDL oxidation by monocytes-macrophages in
vitro are strongly influenced by methodological considerations. These include the presence of metal ion additives, the protection of
LDL during preparation, and the source and treatment of the cells.
There are multiple ways that transition metal ions have been shown to
participate in lipid peroxidation. The hydroxyl radical (·OH)
can be formed by metal ion-dependent processes and can initiate lipid
peroxidation (93, 94); however, transition metals can also catalyze
·OH-independent lipid peroxidation. O Multiple, distinct pathways exist through which
monocytes-macrophages can promote LDL oxidation. Are there clues from
in vivo studies that would aid in discriminating which among
the different mechanisms pertains in vivo? Cp, LO, and MPO
are all abundantly present in lesions (65, 102,
103),4 as perhaps would be
expected considering all have been shown to be enhanced in
monocyte-macrophage systems activated in vitro, and lesions
can be a rich source of macrophages. There is also evidence of LO and
MPO activities in lesions. Non-equilibrium distributions of chiral
fatty acid oxidation products, expected after LO-dependent
oxidation of esterified linoleic acid, have been observed in early
lesions (and less so in later stage lesions) in rabbits (104), as well
as humans (105, 106). Multiple distinct, stable end products of MPO are
enriched both in human vascular lesions and LDL recovered from human
atherosclerotic aortae, including proteins damaged by HOCl (107),
chlorotyrosine (66), dityrosine, and nitrotyrosine (108-110), among
others (71).
Does oxidation involving a metal carrier, as modeled in
vitro using Cp, ferritin, or Zop, take place in vivo?
Because one well characterized pathway for metal-dependent
lipid peroxidation is mediated by ·OH, the absence from early
human atherosclerotic lesions of significant increases in
·OH-generated protein oxidation products (109) has led to the suggestion that metal-mediated LDL oxidation may not take place in vivo (5, 109). However, such a suggestion is tempered
because of known pathways, mentioned above, for ·OH-independent,
metal ion-mediated lipid peroxidation (94, 96). Significant amounts of
·OH-dependent protein oxidation products were
observed in advanced lesions (111).
Does the incidence of atherosclerosis offer hints indicating a
particular oxidative mechanism? Serum Cp was reported to be an
independent risk factor for coronary heart disease (112), and increases
in ultrasound-detectable lesion size correlated with LDL cholesterol
only in subjects with high serum Cp copper levels (113). Furthering the
notion that LO may promote atherosclerosis are one report of a
putatively specific 15-LO inhibitor significantly blunting diet-induced
atherosclerosis in the rabbit (114) and another showing that disruption
of the 12/15-LO gene in apolipoprotein E-deficient mice dramatically
reduced atherosclerosis (115). In surprising contrast, transgenic
rabbits overexpressing macrophage-specific 15-LO were partially
protected from atherosclerosis (116). These apparently conflicting
results have generated cautious evaluation of the role of LO (117,
118).
Despite remaining controversies, cell culture models of
monocyte-macrophage-mediated oxidation of LDL have facilitated the formulation of multiple feasible mechanisms of LDL oxidation and have
generated ideas for intervention in vivo. It is possible that more than one of the mechanisms discussed above pertains in
vivo. Delineation among them awaits more studies of selective inhibition, activation, or overexpression of key proteins such as MPO,
LO, Cp, those required for O
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INTRODUCTION
TOP
INTRODUCTION
The Role of Ceruloplasmin
The Role of O
2
The Role of 15-Lipoxygenase
The Role of Myeloperoxidase
The Role of ·NO...
Methodological Considerations...
Perspectives
REFERENCES
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The Role of Ceruloplasmin
TOP
INTRODUCTION
The Role of Ceruloplasmin
The Role of O
2
The Role of 15-Lipoxygenase
The Role of Myeloperoxidase
The Role of ·NO...
Methodological Considerations...
Perspectives
REFERENCES
2) was
essential for the enhancement of LDL oxidation by Cp under these conditions.
2 and lipoxygenase, both of which are
increased by activation of monocyte-macrophage-related cells. The role
of O
2 may be to reduce the Cp-bound "oxidant" copper
(28).
(36). The observation that a bacterial product
is an agonist may be significant given the possible link between
bacterial infection and atherosclerosis (37). Because T-cells, a major
source of IFN-
, populate arterial lesion sites, Cp accumulation
could be enhanced by a local inflammatory response. However, IFN-
also stimulates antioxidant production by monocytes-macrophages (38)
and has been shown under certain conditions to inhibit LDL oxidation
(39, 40).
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The Role of O
2
TOP
INTRODUCTION
The Role of Ceruloplasmin
The Role of O
2
The Role of 15-Lipoxygenase
The Role of Myeloperoxidase
The Role of ·NO...
Methodological Considerations...
Perspectives
REFERENCES
2 in monocyte-macrophage LDL oxidation is as
debated as that of metal ion, and the two controversies are
interrelated. The dependence on O
2 is less in cell systems in
which the culture medium contains free redox metal ions. Using metal
ion-containing (Ham's F12) medium, Garner et al. (47)
reported O
2-independent LDL oxidation by human
monocytes-macrophages. Our early studies with monocytes-macrophages
were conducted in RPMI 1640 in an effort to mimic the predicted absence
of free metal ions in vivo. Our studies showed that LDL
oxidation required activation of the cells by certain activators,
including opsonized zymosan (Zop) or LPS; other activators were not
effective (14, 32). (Addition of free metal ions to monocytes incubated
in RPMI 1640 resulted in activation-independent LDL oxidation (20).)
The activation dependence in RPMI 1640, the successful inhibition by
numerous antioxidants (14, 32), and the well described enhancement of
O
2 production by monocytes following activation were
consistent with a requirement for O
2. We and others have found
cell-derived, extracellular O
2 to be required, but not
sufficient, for LDL oxidation by monocytes-macrophages (34, 35).
O
2-generating systems alone do not mediate LDL oxidation
(43-45). Others have speculated that superoxide dismutase could be
inhibitory by acting as a metal chelator, rather than a O
2
scavenger, giving the false impression of O
2 dependence (46).
However, further evidence for the requirement for O
2 in this
system is derived from recent studies using in vitro
knockout of p47phox. O
2 and LDL oxidation
were concomitantly ablated when this requisite component of the NADPH
oxidase complex was inhibited by antisense ODN.2
2, which then catalyzes LDL
oxidation, thus putting the Zop-activated cell system into a category
parallel with the concept presented above: that activated
monocytes-macrophages oxidize LDL by a pathway requiring O
2 to
reduce bound transition metal (e.g. Cp-borne cupric or
ferritin-, transferrin-, or hemin-borne ferric).
2 and/or its dismutation product,
H2O2, by monocytes-macrophages appears to be
essential for LDL oxidation in vitro, whether the process is
Cp-, myeloperoxidase- (MPO) (see below), or Zop-dependent.
Accordingly, considerable effort has been devoted to elucidate
signaling pathways regulating the generation of O
2. Multiple
approaches have demonstrated that the pathway for optimal oxidation of
LDL by Zop-activated monocytes-macrophages involved calcium via both
influx and release from intracellular stores (50). Using PKC
inhibitors, down-regulation of PKC expression by PMA, and antisense
ODN, the requirement for activation of the calcium-dependent cPKC isoenzyme, PKC
, was convincingly
shown (51, 52). Selective inhibition of cytosolic phospholipase A2 (cPLA2) using antisense ODN and pharmacological
inhibitors, revealed cPLA2 activity to be another essential
step in the signaling sequence for O
2 production and LDL
oxidation (53). Addition of arachidonic acid, the product of
cPLA2, restored both the production of O
2 and LDL
oxidation (53). Recent data, mentioned above, using p47phox
antisense ODN suggest that the enzymatic source of O
2 is NADPH oxidase. PKC activation may be involved in phosphorylation of various
protein components of this enzyme complex.
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The Role of 15-Lipoxygenase
TOP
INTRODUCTION
The Role of Ceruloplasmin
The Role of O
2
The Role of 15-Lipoxygenase
The Role of Myeloperoxidase
The Role of ·NO...
Methodological Considerations...
Perspectives
REFERENCES
2 (57). O
2 scavengers in a cell-free soybean LO system and
an intracellular O
2 scavenger in an activated
monocyte-macrophage system both enhanced LDL oxidation (57, 60).
Fibroblasts overexpressing 15-LO oxidized LDL moderately more than
control transfected cells (63). Cytokines that modulate 15-LO activity
in Zop-activated monocytes-macrophages (enhancement by interleukin-4
and interleukin-13; inhibition by IFN
) modulated in parallel LDL
oxidation by these cells (64). Angiotensin II enhanced both LO activity
and LDL oxidation in mouse peritoneal macrophages and J774 cells (49). Peritoneal macrophages from animals without 12/15-LO demonstrated impaired LDL oxidation (119). These in vitro studies are
consistent with a contributory role for LO.
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The Role of Myeloperoxidase
TOP
INTRODUCTION
The Role of Ceruloplasmin
The Role of O
2
The Role of 15-Lipoxygenase
The Role of Myeloperoxidase
The Role of ·NO...
Methodological Considerations...
Perspectives
REFERENCES
2, by using it as a co-substrate to
generate a variety of oxidants, including diffusible radical species
(69, 73), reactive halogens (66, 68, 74), aldehydes (70, 75), and
nitrating agents (72, 76-78). The heme group of MPO is buried deep
within a hydrophobic binding pocket and catalyzes the oxidation of a
variety of small substrates that then can diffuse away from the enzyme
and damage cellular targets. Thus, MPO-mediated oxidation reactions
occur in the absence of free transition metal ions and are resistant to
inhibition by chelators. Because of its high concentration in
biological matrices, chloride is regarded as a major substrate for MPO
(79, 80). MPO catalyzes the two-electron oxidation of chloride forming
the powerful oxidant, hypochlorous acid (HOCl). Exposure of LDL to
reagent HOCl results in chlorination and oxidation of protein and lipid
constituents of LDL, induces LDL aggregation, and converts the
lipoprotein into a high uptake form for macrophages (66, 67, 81, 82).
MPO-generated HOCl also oxidizes free
-amino acids, abundant
nutrients in plasma and extracellular fluids, converting them into
aldehydes (70, 75, 83, 84). MPO-generated aldehydes can then modify
nucleophilic targets on LDL protein and lipids (85, 86). In addition,
MPO can catalyze the one-electron oxidation of L-tyrosine,
generating the tyrosyl radical. PMA-activated phagocytes can produce
tyrosyl radical and initiate LDL lipid peroxidation and dityrosine
cross-linking of proteins (69, 73).
), a major end product of nitric
oxide (nitrogen monoxide, ·NO) metabolism, to generate a
reactive intermediate capable of nitrating aromatic compounds and
tyrosine residues (77, 78, 87). In addition, HOCl can react with
NO2
to form a nitrating
and chlorinating intermediate (76). Recent studies demonstrate that
exposure of LDL to NO2
and either
elutriated human monocytes or isolated MPO and an H2O2 source results in LDL lipid peroxidation
and protein nitration (72). Moreover, LDL modified by MPO-generated
nitrating intermediates is rendered a ligand for high affinity binding
and uptake by macrophages, resulting in cholesteryl ester accumulation
and foam cell formation (72). The biological consequences of LDL
modification by MPO-generated chlorinating intermediates, reactive
aldehydes, nitrating intermediates, and diffusible radical species are
areas for future study.
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The Role of ·NO and ·NO-derived Oxidants
TOP
INTRODUCTION
The Role of Ceruloplasmin
The Role of O
2
The Role of 15-Lipoxygenase
The Role of Myeloperoxidase
The Role of ·NO...
Methodological Considerations...
Perspectives
REFERENCES
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Methodological Considerations Affecting Mechanisms of
Oxidation
TOP
INTRODUCTION
The Role of Ceruloplasmin
The Role of O
2
The Role of 15-Lipoxygenase
The Role of Myeloperoxidase
The Role of ·NO...
Methodological Considerations...
Perspectives
REFERENCES
2 and
H2O2 support metal-catalyzed lipid peroxidation
through their participation in redox reactions, e.g. as a
reductant for Fe3+ and as an oxidant for Fe2+,
respectively (93, 95). Fe2+ can also react with preformed lipid
hydroperoxides to generate lipid alkoxyl radicals and facilitate lipid
peroxidation (96). Thus LDL that carries even minor amounts of lipid
hydroperoxides will be more susceptible to metal ion-mediated oxidation
(97, 98). Trace levels of hydroperoxides may be formed in
vivo and circulate on lipoproteins, or they may arise from
spurious oxidation during isolation and storage. LDL will also readily
bind LPS, altering (sometimes dramatically) the outcomes of LDL-cell
interactions (99). The cell isolation method also influences the
pathways involved in monocyte-macrophage-dependent oxidation of
LDL. For example, protocols that employ adhesion of monocytes in
vitro, both to simulate adherence in vivo and to
facilitate removal of other mononuclear cells, can lead to release of
granule contents, including
MPO.3 Human monocyte-derived
macrophages generated in culture also lose MPO during differentiation
unless grown in the presence of specific growth factors and cytokines
(100, 101). Thus, the role of MPO-dependent oxidation
events can best be studied in fresh monocytes isolated by methods that
do not require adhesion, such as buoyant density centrifugation or elutriation.
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Perspectives
TOP
INTRODUCTION
The Role of Ceruloplasmin
The Role of O
2
The Role of 15-Lipoxygenase
The Role of Myeloperoxidase
The Role of ·NO...
Methodological Considerations...
Perspectives
REFERENCES
2 generation, or perhaps extracellularly active forms of superoxide dismutase or catalase.
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FOOTNOTES |
|---|
* This minireview will be reprinted in the 1999 Minireview Compendium, which will be available in December, 1999. This is the fifth article of five in "A Thematic Series on Oxidation of Lipids as a Source of Messengers." Support is acknowledged from National Institutes of Health Grants HL29582, HL51068, HL61971, and HL62526.
To whom correspondence should be addressed: Dept. of Cell Biology,
Lerner Research Inst., Cleveland Clinic Foundation (NC 10), 9500 Euclid
Ave., Cleveland, OH 44195. Tel.: 216-444-5854; Fax: 216-444-9404;
E-mail: chisolg@ccf.org.
2 E. Bey and M. K. Cathcart, submitted for publication.
3 S. L. Hazen and M. K. Cathcart, unpublished observations.
4 E. Ehrenwald and P. L. Fox, unpublished observations.
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ABBREVIATIONS |
|---|
The abbreviations used are:
LDL, low density
lipoprotein;
Cp, ceruloplasmin;
EC, endothelial cell;
IFN, interferon;
LO, lipoxygenase;
LPS, lipopolysaccharide;
MPO, myeloperoxidase;
O
2, superoxide anion;
ODN, oligodeoxyribonucleotide(s);
·NO, nitrogen monoxide (nitric oxide);
PKC, protein kinase C;
cPKC, conventional PKC;
cPLA2, cytosolic phospholipase
A2;
PMA, phorbol myristate acetate;
SMC, smooth muscle
cell;
Zop, opsonized zymosan.
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REFERENCES |
|---|
2
|
|---|
| 1. | Chisolm, G. M., and Penn, M. S. (1996) in Oxidized Lipoproteins and Atherosclerosis (Fuster, V. , Ross, R. , and Topol, E. J., eds) , pp. 129-149, Raven Press, New York |
| 2. |
Steinberg, D.
(1997)
J. Biol. Chem.
272,
20963-20966 |
| 3. | Berliner, J. A., Navab, M., Fogelman, A. M., Frank, J. S., Demer, L. L., Edwards, P. A., Watson, A. D., and Lusis, A. J. (1995) Circulation 91, 2488-2496[Medline] [Order article via Infotrieve] |
| 4. |
Witztum, J. L.,
and Horkko, S.
(1997)
Ann. N. Y. Acad. Sci.
811,
88-99 |
| 5. | Heinecke, J. W. (1998) Atherosclerosis 141, 1-15[Medline] [Order article via Infotrieve] |
| 6. | Yla-Herttuala, S. (1998) Curr. Opin. Lipidol. 9, 337-344[CrossRef][Medline] [Order article via Infotrieve] |
| 7. | Hessler, J. R., Robertson, A. L., Jr., and Chisolm, G. M. (1979) Atherosclerosis 32, 213-229[CrossRef][Medline] [Order article via Infotrieve] |
| 8. | Hessler, J. R., Morel, D. W., Lewis, L. J., and Chisolm, G. M. (1983) Arteriosclerosis 3, 215-222[Abstract] |
| 9. | Morel, D. W., Hessler, J. R., and Chisolm, G. M. (1983) J. Lipid Res. 24, 1070-1076[Abstract] |
| 10. | Henriksen, T., Mahoney, E. M., and Steinberg, D. (1983) Arteriosclerosis 3, 149-159[Abstract] |
| 11. |
Henriksen, T.,
Mahoney, E. M.,
and Steinberg, D.
(1981)
Proc. Natl. Acad. Sci. U. S. A.
78,
6499-6503 |
| 12. |
Steinbrecher, U. P.,
Parthasarathy, S.,
Leake, D. S.,
Witztum, J. L.,
and Steinberg, D.
(1984)
Proc. Natl. Acad. Sci. U. S. A.
81,
3883-3887 |
| 13. | Morel, D. W., DiCorleto, P. E., and Chisolm, G. M. (1984) Arteriosclerosis 4, 357-364[Abstract] |
| 14. | Cathcart, M. K., Morel, D. W., and Chisolm, G. M. (1985) J. Leukocyte Biol. 38, 341-350[Abstract] |
| 15. | Dabbagh, A. J., and Frei, B. (1995) J. Clin. Invest. 96, 1958-1966 |
| 16. | Aasa, R., Malmstrom, B. G., Saltman, P., and Vangard, T. (1963) Biochim. Biophys. Acta 75, 203-222[Medline] [Order article via Infotrieve] |
| 17. | Thomas, C. E. (1992) Biochim. Biophys. Acta 1128, 50-57[Medline] [Order article via Infotrieve] |
| 18. | Heinecke, J. W., Rosen, H., and Chait, A. (1984) J. Clin. Invest. 74, 1890-1894 |
| 19. | Tangirala, R. K., Mol, M. J., and Steinberg, D. (1996) J. Lipid Res. 37, 835-843[Abstract] |
| 20. | Cathcart, M. K., Li, Q., and Chisolm, G. M. (1995) J. Lipid Res. 36, 1857-1865[Abstract] |
| 21. | Aviram, M., and Rosenblat, M. (1994) J. Lipid Res. 35, 385-398[Abstract] |
| 22. | Ehrenwald, E., Chisolm, G. M., and Fox, P. L. (1994) J. Clin. Invest. 93, 1493-1501 |
| 23. | Ehrenwald, E., and Fox, P. L. (1994) Arch. Biochem. Biophys. 309, 392-395[CrossRef][Medline] [Order article via Infotrieve] |
| 24. | Van Lenten, B. J., Hama, S. Y., de Beer, F. C., Stafforini, D. M., McIntyre, T. M., Prescott, S. M., La Du, B. N., Fogelman, A. M., and Navab, M. (1995) J. Clin. Invest. 96, 2758-2767 |
| 25. | Lamb, D. J., and Leake, D. S. (1994) FEBS Lett. 338, 122-126[CrossRef][Medline] [Order article via Infotrieve] |
| 26. | Swain, J. A., Darley-Usmar, V., and Gutteridge, J. M. (1994) FEBS Lett. 342, 49-52[CrossRef][Medline] [Order article via Infotrieve] |
| 27. |
Mukhopadhyay, C. K.,
Ehrenwald, E.,
and Fox, P. L.
(1996)
J. Biol. Chem.
271,
14773-14778 |
| 28. | Mukhopadhyay, C. K., and Fox, P. L. (1998) Biochemistry 37, 14222-14229[CrossRef][Medline] [Order article via Infotrieve] |
| 29. |
Mukhopadhyay, C. K.,
Mazumder, B.,
Lindley, P. F.,
and Fox, P. L.
(1997)
Proc. Natl. Acad. Sci. U. S. A.
94,
11546-11551 |
| 30. |
Yang, F. M.,
Friedrichs, W. E.,
Cupples, R. L.,
Bonifacio, M. J.,
Sanford, J. A.,
Horton, W. A.,
and Bowman, B. H.
(1990)
J. Biol. Chem.
265,
10780-10785 |
| 31. |
Fleming, R. E.,
Whitman, I. P.,
and Gitlin, J. D.
(1991)
Am. J. Physiol.
260,
L68-L74 |
| 32. | Cathcart, M. K., Chisolm, G. M., McNally, A. K., and Morel, D. W. (1988) In Vitro Cell. Dev. Biol. 24, 1001-1008[Medline] [Order article via Infotrieve] |
| 33. | Ehrenwald, E., and Fox, P. L. (1996) J. Clin. Invest. 97, 884-890[Medline] [Order article via Infotrieve] |
| 34. | Cathcart, M. K., McNally, A. K., Morel, D. W., and Chisolm, G. M. (1989) J. Immunol. 142, 1963-1969[Abstract] |
| 35. | Hiramatsu, K., Rosen, H., Heinecke, J. W., Wolfbauer, G., and Chait, A. (1987) Arteriosclerosis 7, 55-60[Abstract] |
| 36. | Mazumder, B., Mukhopadhyay, C. K., Prok, A., Cathcart, M. K., and Fox, P. L. (1997) J. Immunol. 159, 1938-1944[Abstract] |
| 37. | Libby, P., Egan, D., and Skarlatos, S. (1997) Circulation 96, 4095-4103[Medline] [Order article via Infotrieve] |
| 38. | Christen, S., Thomas, S. R., Garner, B., and Stocker, R. (1994) J. Clin. Invest. 93, 2149-2158 |
| 39. | Fong, L. G., Albert, T. S., and Hom, S. E. (1994) J. Lipid Res. 35, 893-904[Abstract] |
| 40. | Folcik, V. A., and Cathcart, M. K. (1994) J. Lipid Res. 35, 1570-1582[Abstract] |
| 41. |
Camejo, G.,
Halberg, C.,
Manschik-Lundin, A.,
Hurt-Camejo, E.,
Rosengren, B.,
Olsson, H.,
Hansson, G. I.,
Forsberg, G. B.,
and Ylhen, B.
(1998)
J. Lipid Res.
39,
755-766 |
| 42. | Abdalla, D. S. P., Campa, A., and Monteiro, H. P. (1992) Atherosclerosis 97, 149-159[CrossRef][Medline] [Order article via Infotrieve] |
| 43. | Lynch, S. M., and Frei, B. (1993) J. Lipid Res. 34, 1745-1753[Abstract] |
| 44. | Bedwell, S., Dean, R. T., and Jessup, W. (1989) Biochem. J. 262, 707-712[Medline] [Order article via Infotrieve] |
| 45. | Bonnefont-Rousselot, D., Gardès-Albert, M., Lepage, S., Delattre, J., and Ferradini, C. (1992) Radiat. Res. 132, 228-236[CrossRef][Medline] [Order article via Infotrieve] |
| 46. | Jessup, W., Simpson, J. A., and Dean, R. T. (1993) Atherosclerosis 99, 107-120[CrossRef][Medline] [Order article via Infotrieve] |
| 47. | Garner, B., Dean, R. T., and Jessup, W. (1994) Biochem. J. 301, 421-428 |
| 48. |
Xing, X.,
Baffic, J.,
and Sparrow, C. P.
(1998)
J. Lipid Res.
39,
2201-2208 |
| 49. |
Scheidegger, K. J.,
Butler, S.,
and Witztum, J. L.
(1997)
J. Biol. Chem.
272,
21609-21615 |
| 50. | Li, Q., Tallant, A., and Cathcart, M. K. (1993) J. Clin. Invest. 91, 1499-1506 |
| 51. |
Li, Q.,
and Cathcart, M. K.
(1994)
J. Biol. Chem.
269,
17508-17515 |
| 52. |
Li, Q.,
Subbulakshmi, V.,
Fields, A. P.,
Murray, N. R.,
and Cathcart, M. K.
(1999)
J. Biol. Chem.
274,
3764-3771 |
| 53. |
Li, Q.,
and Cathcart, M. K.
(1997)
J. Biol. Chem.
272,
2404-2411 |
| 54. |
Parthasarathy, S.,
Wieland, E.,
and Steinberg, D.
(1989)
Proc. Natl. Acad. Sci. U. S. A.
86,
1046-1050 |
| 55. |
Belkner, J.,
Stender, H.,
and Kuhn, H.
(1998)
J. Biol. Chem.
273,
23225-23232 |
| 56. | Sparrow, C. P., Parthasarathy, S., and Steinberg, D. (1988) J. Lipid Res. 29, 745-753[Abstract] |
| 57. | Cathcart, M. K., McNally, A. K., and Chisolm, G. M. (1991) J. Lipid Res. 32, 63-70[Abstract] |
| 58. | Folcik, V. A., and Cathcart, M. K. (1993) J. Lipid Res. 34, 69-79[Abstract] |
| 59. | Jessup, W., Darley-Usmar, V. M., O'Leary, V., and Bedwell, S. (1991) Biochem. J. 278, 163-169 |
| 60. | McNally, A. K., Chisolm, G. M., Morel, D. W., and Cathcart, M. K. (1990) J. Immunol. 145, 254-259[Abstract] |
| 61. |
Sparrow, C. P.,
and Olszewski, J.
(1992)
Proc. Natl. Acad. Sci. U. S. A.
89,
128-131 |
| 62. | Rankin, S. M., Parthasarathy, S., and Steinberg, D. (1991) J. Lipid Res. 32, 449-456[Abstract] |
| 63. |
Sigari, F.,
Lee, C.,
Witztum, J. L.,
and Reaven, P. D.
(1997)
Arterioscler. Thromb. Vasc. Biol.
17,
3639-3645 |
| 64. |
Folcik, V. A.,
Aamir, R.,
and Cathcart, M. K.
(1997)
Arterioscler. Thromb. Vasc. Biol.
17,
1954-1961 |
| 65. | Daugherty, A., Dunn, J. L., Rateri, D. L., and Heinecke, J. W. (1994) J. Clin. Invest. 94, 437-444 |
| 66. | Hazen, S. L., and Heinecke, J. W. (1997) J. Clin. Invest. 99, 2075-2081[Medline] [Order article via Infotrieve] |
| 67. |
Hazen, S. L.,
Hsu, F. F.,
Duffin, K.,
and Heinecke, J. W.
(1996)
J. Biol. Chem.
271,
23080-23088 |
| 68. | Hazen, S. L., Hsu, F. F., Mueller, D. M., Crowley, J. R., and Heinecke, J. W. (1996) J. Clin. Invest. 98, 1283-1289[Medline] [Order article via Infotrieve] |
| 69. |
Heinecke, J. W.,
Li, W.,
Daehnke, H. L., III,
and Goldstein, J. A.
(1993)
J. Biol. Chem.
268,
4069-4077 |
| 70. | Hazen, S. L., Hsu, F. F., d'Avignon, A., and Heinecke, J. W. (1998) Biochemistry 37, 6864-6873[CrossRef][Medline] [Order article via Infotrieve] |
| 71. | Heinecke, J. W. (1997) Biofactors 6, 145-155[Medline] [Order article via Infotrieve] |
| 72. | Podrez, E. A., Schmitt, D., Hoff, H. F., and Hazen, S. L. (1999) J. Clin. Invest. 103, 1547-1560[Medline] [Order article via Infotrieve] |
| 73. |
Savenkova, M. L.,
Mueller, D. M.,
and Heinecke, J. W.
(1994)
J. Biol. Chem.
269,
20394-20400 |
| 74. | Hurst, J. K., and Barrette, W. C., Jr. (1989) Crit. Rev. Biochem. Mol. Biol. 24, 271-328 |
| 75. |
Hazen, S. L.,
d'Avignon, A.,
Anderson, M. M.,
Hsu, F. F.,
and Heinecke, J. W.
(1998)
J. Biol. Chem.
273,
4997-5005 |
| 76. |
Eiserich, J. P.,
Cross, C. E.,
Jones, A. D.,
Halliwell, B.,
and van der Vliet, A.
(1996)
J. Biol. Chem.
271,
19199-19208 |
| 77. |
van der Vliet, A.,
Eiserich, J. P.,
Halliwell, B.,
and Cross, C. E.
(1997)
J. Biol. Chem.
272,
7617-7625 |
| 78. | Eiserich, J. P., Hristova, M., Cross, C. E., Jones, A. D., Freeman, B. A., Halliwell, B., and van der Vliet, A. (1998) Nature 391, 393-397[CrossRef][Medline] [Order article via Infotrieve] |
| 79. |
Harrison, J. E.,
and Schultz, J.
(1976)
J. Biol. Chem.
251,
1371-1374 |
| 80. |
Lampert, M. B.,
and Weiss, S. J.
(1983)
Blood
62,
645-651 |
| 81. | Hazell, L. J., and Stocker, R. (1993) Biochem. J. 290, 165-172 |
| 82. | Hazell, L. J., van den Berg, J. J., and Stocker, R. (1994) Biochem. J. 302, 297-304 |
| 83. |
Hazen, S. L.,
Hsu, F. F.,
and Heinecke, J. W.
(1996)
J. Biol. Chem.
271,
1861-1867 |
| 84. | Anderson, M. M., Hazen, S. L., Hsu, F. F., and Heinecke, J. W. (1997) J. Clin. Invest. 99, 424-432[Medline] [Order article via Infotrieve] |
| 85. |
Hazen, S. L.,
Gaut, J. P.,
Hsu, F. F.,
Crowley, J. R.,
d'Avignon, A.,
and Heinecke, J. W.
(1997)
J. Biol. Chem.
272,
16990-16998 |
| 86. | Hazen, S. L., Heller, J., Hsu, F. F., d'Avegnon, A., and Heinecke, J. W. (1998) Chem. Res. Toxicol. 12, 19-27 |
| 87. |
Jiang, Q.,
and Hurst, J. K.
(1997)
J. Biol. Chem.
272,
32767-32772 |
| 88. |
Moncada, S.,
and Higgs, A.
(1993)
N. Engl. J. Med.
329,
2002-2012 |
| 89. | Jessup, W., Mohr, D., Gieseg, S. P., Dean, R. T., and Stocker, R. (1992) Biochim. Biophys. Acta 1180, 73-82[Medline] [Order article via Infotrieve] |
| 90. |
Beckman, J. S.,
and Koppenol, W. H.
(1996)
Am. J. Physiol.
271,
C1424-C1437 |
| 91. | Patel, R. P., McAndrew, J., Sellak, H., White, C. R., Jo, H., Freeman, B. A., and Darley-Usmar, V. M. (1999) Biochim. Biophys. Acta 1411, 385-400[Medline] [Order article via Infotrieve] |
| 92. | Hogg, N., and Kalyanaraman, B. (1999) Biochim. Biophys. Acta 1411, 378-384[Medline] [Order article via Infotrieve] |
| 93. | Miller, D. M., Grover, T. A., Nayini, N., and Aust, S. D. (1993) Arch. Biochem. Biophys. 301, 1-7[CrossRef][Medline] [Order article via Infotrieve] |
| 94. | Minotti, G., and Aust, S. D. (1989) Chem. Biol. Interact. 71, 1-19[CrossRef][Medline] [Order article via Infotrieve] |
| 95. | Aust, S. D. (1995) Toxicol. Lett. 82-83, 941-944[CrossRef] |
| 96. | Minotti, G., and Aust, S. D. (1992) Lipids 27, 219-226[Medline] [Order article via Infotrieve] |
| 97. | Frei, B., and Gaziano, J. M. (1993) J. Lipid Res. 34, 2135-2145[Abstract] |
| 98. |
Thomas, C. E.,
and Jackson, R. L.
(1991)
J. Pharmacol. Exp. Ther.
256,
1182-1188 |
| 99. | Morel, D. W., DiCorleto, P. E., and Chisolm, G. M. (1986) Lab. Invest. 55, 419-426[Medline] [Order article via Infotrieve] |
| 100. | Tsuruta, T., Tani, K., Shimane, M., Ozawa, K., Takahashi, S., Tsuchimoto, D., Takahashi, K., Nagata, S., Sato, N., and Asano, S. (1996) Br. J. Haematol. 92, 9-22[CrossRef][Medline] [Order article via Infotrieve] |
| 101. | Pickl, W. F., Majdic, O., Kohl, P., Stockl, J., Riedl, E., Scheinecker, C., Bello-Fernandez, C., and Knapp, W. (1996) J. Immunol. 157, 3850-3859[Abstract] |
| 102. |
Yla-Herttuala, S.,
Rosenfeld, M. E.,
Parthasarathy, S.,
Glass, C. K.,
Sigal, E.,
Witztum, J. L.,
and Steinberg, D.
(1990)
Proc. Natl. Acad. Sci. U. S. A.
87,
6959-6963 |
| 103. | Swain, J., and Gutteridge, J. M. (1995) FEBS Lett. 368, 513-515[CrossRef][Medline] [Order article via Infotrieve] |
| 104. |
Kuhn, H.,
Belkner, J.,
Zaiss, S.,
Fahrenklemper, T.,
and Wohlfeil, S.
(1994)
J. Exp. Med.
179,
1903-1911 |
| 105. | Folcik, V. A., Nivar-Aristy, R. A., Krajewski, L. P., and Cathcart, M. K. (1995) J. Clin. Invest. 96, 504-510 |
| 106. | Kuhn, H., Heydeck, D., Hugou, I., and Gniwotta, C. (1997) J. Clin. Invest. 99, 888-893[Medline] [Order article via Infotrieve] |
| 107. | Hazell, L. J., Arnold, L., Flowers, D., Waeg, G., Malle, E., and Stocker, R. (1996) J. Clin. Invest. 97, 1535-1544[Medline] [Order article via Infotrieve] |
| 108. |
Leeuwenburgh, C.,
Hardy, M. M.,
Hazen, S. L.,
Wagner, P.,
Oh-ishi, S.,
Steinbrecher, U. P.,
and Heinecke, J. W.
(1997)
J. Biol. Chem.
272,
1433-1436 |
| 109. |
Leeuwenburgh, C.,
Rasmussen, J. E.,
Hsu, F. F.,
Mueller, D. M.,
Pennathur, S.,
and Heinecke, J. W.
(1997)
J. Biol. Chem.
272,
3520-3526 |
| 110. | Beckman, J. S., Ye, Y. Z., Anderson, P. G., Chen, J., Accavitti, M. A., Tarpey, M. M., and White, C. R. (1994) Biol. Chem. Hoppe-Seyler 375, 81-88[Medline] [Order article via Infotrieve] |
| 111. | Fu, S., Fu, M. X., Baynes, J. W., Thorpe, S. R., and Dean, R. T. (1998) Biochem. J. 330, 233-239 |
| 112. |
Manttari, M.,
Manninen, V.,
Huttunen, J. K.,
Palosuo, T.,
Ehnholm, C.,
Heinonen, O. P.,
and Frick, M. H.
(1994)
Eur. Heart J.
15,
1599-1603 |
| 113. | Salonen, J. T., Salonen, R., Seppänen, K., Kantola, M., Suntioinen, S., and Korpela, H. (1991) Br. Med. J. 302, 756-760 |
| 114. | Bocan, T. M., Rosebury, W. S., Mueller, S. B., Kuchera, S., Welch, K., Daugherty, A., and Cornicelli, J. A. (1998) Atherosclerosis 136, 203-216[CrossRef][Medline] [Order article via Infotrieve] |
| 115. | Cyrus, T., Witztum, J. L., Rader, D. J., Tangirala, R., Fazio, S., Linton, M. F., and Funk, C. D. (1999) J. Clin. Invest. 103, 1597-1604[Medline] [Order article via Infotrieve] |
| 116. | Shen, J., Herderick, E., Cornhill, J. F., Zsigmond, E., Kim, H. S., Kuhn, H., Guevara, N. V., and Chan, L. (1996) J. Clin. Invest. 98, 2201-2208[Medline] [Order article via Infotrieve] |
| 117. | Kuhn, H., and Chan, L. (1997) Curr. Opin. Lipidol. 8, 111-117[CrossRef][Medline] [Order article via Infotrieve] |
| 118. | Steinberg, D. (1999) J. Clin. Invest. 103, 1487-1488[Medline] [Order article via Infotrieve] |
| 119. |
Sun, D.,
and Funk, C. D.
(1996)
J. Biol. Chem.
271,
24055-24062 |
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