© 1999 American Heart Association, Inc.
Atherosclerosis and Lipoproteins |
Role of Group II Secretory Phospholipase A2 in Atherosclerosis
1. Increased Atherogenesis and Altered Lipoproteins in Transgenic Mice Expressing Group IIa Phospholipase A2
From the Department of Microbiology and Molecular Genetics and Molecular Biology Institute (B.I., L.C., X.-P.W., J.-H.Q., M.M., A.J.L.), and the Department of Medicine, Division of Cardiology (B.I., L.C., X.-P.W., J.-H.Q., M.M., M.N., A.M.F., A.J.L.), University of California, Los Angeles; Chrysalis DNX Transgenic Sciences (D.S.G., M.E.S.), Princeton, New Jersey; and the Department of Internal Medicine and Biochemistry (M.C.d.B., F.d.B.), University of Kentucky, Lexington.
Correspondence to Aldons J. Lusis, Department Medicine, UCLA School of Medicine, Los Angeles, CA 90095.
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Abstract—Some observations have suggested that the extracellular group IIa phospholipase A2 (sPLA2), previously implicated in chronic inflammatory conditions such as arthritis, may contribute to atherosclerosis. We have examined this hypothesis by studying transgenic mice expressing the human enzyme. Compared with nontransgenic littermates, the transgenic mice exhibited dramatically increased atherosclerotic lesions when maintained on a high-fat, high-cholesterol diet. Surprisingly, the transgenic mice also exhibited significant atherosclerotic lesions when maintained on a low-fat chow diet. Immunohistochemical staining indicated that sPLA2 was present in the atherosclerotic lesions of the transgenic mice. On both chow and atherogenic diets, the transgenic mice exhibited decreased levels of HDLs and slightly increased levels of LDLs compared with nontransgenic littermates. These data indicate that group IIa sPLA2 may promote atherogenesis, in part, through its effects on lipoprotein levels. These data also provide a possible mechanism for the observation that there is an increased incidence of coronary artery disease in many chronic inflammatory diseases.
Key Words: inflammation • lipoproteins • paraoxonase
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Introduction |
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Phospholipase A2 (PLA2) enzymes catalyze the hydrolysis of the sn-2 fatty acyl ester bonds of phospholipids to produce a free fatty acid, often arachidonic acid, and a lysophospholipid.1 2 Several different species of PLA2 have been recognized in mammals.3 Most extensively studied are the pancreatic enzymes functioning in digestion (group I) and a low molecular weight (14 kDa) soluble species of PLA2 widely expressed in different tissues (group II). The release of arachidonic acid, by both cellular and extracellular PLA2s, is rate limiting in the generation of various oxidation products of arachidonic acid, including prostaglandins, thromboxanes, and leukotrienes.4 5 The secreted group IIa PLA2 (sPLA2) has been shown to stimulate oxidation of LDL by lipoxygenase.6 Lysophospholipids, on the other hand, can influence cellular functions7 and can be further processed to produce platelet-activating factor.6
Grass et al8 previously reported the development of
lines of transgenic mice expressing the entire human group IIa
sPLA2 gene. The pattern of expression of the
enzyme resembled that of the human enzyme, with expression in almost
all tissues examined and highest levels of expression in liver, lung,
skin, and kidney. The sPLA2 activity in serum was
elevated 
8-fold compared with nontransgenic mice. The transgenic
mice did not exhibit inflammatory infiltrates in various tissues
examined, although they exhibited epidermal hyperplasia.
Because sPLA2 is found in human atherosclerotic lesions9 10 and a variety of in vitro studies suggest that the enzyme can promote inflammation,2 we have examined the sPLA2 transgenic mice for susceptibility to diet-induced atherogenesis. For these studies, the transgene was transferred by repeated backcrossing to the atherosclerosis-susceptible C57BL/6J inbred strain. This strain exhibits a naturally occurring null mutation of the group IIa sPLA2 gene, providing a clear contrast for the effects of the transgene.11 Our results reveal that the transgenic mice exhibit dramatically increased atherosclerosis when fed an atherogenic diet. The lipoprotein profiles of the transgenic mice appeared to be more pro-atherogenic than those of nontransgenic littermates, and the transgenic mice exhibited markedly reduced levels of paraoxonase, an enzyme associated with HDL that protects against LDL oxidation.
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Methods |
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Animals
Mice were obtained from Chrysalis DNX Transgenic sciences (Princeton, NJ). The sPLA2 transgenic mice were produced by microinjection of a 6.2-kb HindIII restriction fragment containing the human secretory PLA2 gene into (B6xSJL)F2 hybrid embryos, which were transferred to strain ICR recipients and developed to term according to standard protocols.8 The transgene contained the complete gene with 1.6 kb of 5'-flanking and 0.35 kb of 3'-flanking genomic sequence, permitting the regulation of the transgene by its natural promoter.8 The sPLA2 transgenic mice were backcrossed repeatedly (for at least 4 generations) to C57BL/6J mice. The genomes of the resulting experimental mice, both transgenic and nontransgenic littermates, were thus derived primarily (>90% on average) from the parental C57BL/6J mice. Transfer of lines onto the C57BL/6J background had the advantage of increasing the susceptibility to diet-induced atherosclerosis in these mice. Also, C57BL/6J mice have a natural null mutation for mouse sPLA2, which facilitates studies of the effects of the human transgene.11 All animals were maintained in a barrier facility with equal light/dark cycle and free access to water and food. At 4 to 6 months of age some animals were maintained for 12 weeks on an atherogenic diet containing 1.25% cholesterol, 15.75% fat, and 0.5% sodium cholate (TD 90221, Harlan-Teklad, Madison, WI). Both before and after the high-fat diet challenge, blood samples were collected from the overnight-fasted mice by bleeding through the retro-orbital sinus after anesthesia with isofluorane, using heparin (3.0 U/mL blood) as an anticoagulant. At the end of the experimental period, mice were anesthetized with isoflurane and euthanized by cervical dislocation. All animal procedures were carried out according to the regulations of the University of California Animal Research Committee.
Histological Analyses
After the mice were killed, the heart and proximal aorta
were excised and washed in PBS. The apex and lower half of the
ventricle were cut off. The remaining specimen was embedded in
Tissue-Tek (Miles), frozen on dry ice, and stored at -70°C until
sectioning. Serial cryosections were prepared through the ventricle
until the aortic valves appeared. From then on, every other 10-µm
section was collected on poly-D-lysine–coated slides until
the aortic sinus was completely sectioned. Sections were stained with
hematoxylin and oil red O, which specifically stains
lipids.12 Slides were examined by light microscopy. The
average fatty streak lesion area was quantified throughout the aortic
sinus using an ocular with a µm2 grid and
was normalized to 40 sections according to protocols previously
published.12 Immunohistochemical staining was performed as
described previously12 using an avidin-biotinylated
peroxidase system (ABC kit, Vector and AEC kit; Biomeda Corp). We used
a monospecific polyclonal rabbit anti-human sPLA2
antiserum (F.C. de Beer, unpublished) as the primary antibody. This
antibody was a gift from Dr Jeff Browning, Biogen Inc, Cambridge, MA,
and was prepared using recombinant human sPLA2
expressed in CHO cells. As judged by Western blotting, it was
monospecific. For example, a single 14 kDa band was observed by Western
blotting of extracts of CHO cells expressing recombinant group II
sPLA2, whereas no signal was obtained with
control CHO cells (data not shown). The optimal dilution used for the
antiserum to sPLA2 was 1:200. Controls included
the omission of primary antibody and the use of frozen sections of
aortic tissues from nontransgenic littermates fed the atherogenic
diet.
Lipids and Lipoproteins
Plasma esterified and unesterified cholesterol and
plasma triglycerides, glycerol, and free fatty acid
concentrations were measured using colorimetric assays
as described previously.13 LDL (d=1.019 to
1.063 g/mL) and HDL (d=1.063 to 1.210 g/mL) were isolated
from plasma by sequential density
ultracentrifugation13 14 in the
absence of EDTA to avoid inactivation of paraoxonase. These
preparations were judged to be at least 95% pure as determined by gel
electrophoresis. In addition, mouse HDL-containing fractions were
isolated from pooled plasma by fast protein liquid
chromatography (FPLC).13 Protein content
was measured using a microtiter plate assay.15 16
Paraoxonase Activity
Pooled plasma samples and FPLC fractions were assayed for
paraoxonase activity using paraoxon as substrate.17 18 The
cuvette contained 1.0 mmol/L paraoxon in 20 mmol/L Tris-HCl,
pH 8.0. The reaction was initiated by the addition of the lipoprotein
sample and the increase in the absorbance at 405 nm was recorded
for 90 seconds. Blanks were included to correct for the spontaneous
hydrolysis of paraoxon. Enzymatic activity was calculated from the
molar extinction coefficient 13 100 mol ·
L-1 · cm-1. A
unit of paraoxonase activity is defined as 1 nmol of 4-nitrophenol
formed per minute under the above assay conditions.17
Statistical Methods
Data analysis (Mann-Whitney U Test) was
performed using the StatView (Abacus Concepts Inc) program.
Significance levels were set to P<0.05 and not corrected
for multiple comparisons. All measurements were done at least in
triplicate, unless indicated otherwise.
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Results |
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sPLA2 Expression in Transgenic Mice
Grass et al8 previously examined the expression of sPLA2 in transgenic mice and observed a pattern similar to human sPLA2, with expression in most tissues. The background C57BL/6J strain mice have a naturally occurring null mutation of the group IIa sPLA2 and, therefore, lack enzyme activity. We utilized immunohistochemical staining with a rabbit polyclonal antibody to examine sPLA2 presence in certain tissues relevant to our studies, including arterial vessels and liver, on both chow and high-fat diets. As shown in Figure 1
, positive staining for sPLA2 was observed in
atherosclerotic lesions of the aorta of transgenic mice but not in the
lesions of nontransgenic controls. Little or no staining of
sPLA2 was observed in normal arteries of either
transgenic or nontransgenic mice (data not shown).
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Increased Aortic Fatty Streak Lesions in sPLA2
Transgenic Mice Maintained on a High-Fat Diet
Adult sPLA2 transgenic mice and their
nontransgenic littermates, both of a strain C57BL/6J genetic
background, were challenged for 12 weeks with a high-fat,
high-cholesterol "atherogenic" diet. After euthanasia,
the hearts, along with the proximal aorta, were dissected, sectioned,
and stained as previously described.12 Fatty streak
lesions were observed as intimal lipid deposits appearing red after
staining with oil red O (Figure 2). More
advanced lesion stages of a fibroproliferative type or extending beyond
the aortic sinus were not observed. The total lesion areas of male
transgenic animals were 6-fold greater than those of nontransgenic
male littermates and the lesion areas of female transgenic mice were
about twice those of female littermates (Figure 3). The absolute increase in lesion size
resulting from the transgene was similar in males and females (Figure 3). These differences were significant in transgenic mice
compared with control mice irrespective of gender (P=0.0006
in all, P=0.0011 in male, and P=0.0046 in female
mice, Figure 2). The average lesion area in the female mice was
significantly greater than in male mice (P=0.0046 in
transgenic and P<0.0001 in nontransgenic littermates), a
phenomenon observed in most mouse models, including apolipoprotein E
knockout mice (see Discussion).
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Spontaneous Aortic Fatty Streak Lesions in sPLA2
Transgenic Mice Maintained on a Low-Fat Chow Diet
Because of the very significant increase in lesions in transgenic
sPLA2 mice compared with nontransgenic
littermates, we examined aortic lesions in 6-month-old mice maintained
on a low-fat chow diet. We observed significant lesions in all 7
transgenic females examined, whereas 7 control female C57BL/6J mice
exhibited no lesions or very small lesions (Figure 4). The average lesion size of the
transgenic mice was 790±294 µm2/section
and that of the nontransgenic mice was 18±18
µm2/section (P<0.03). The finding
of such spontaneous lesions was surprising, given the relatively low
levels of LDL/VLDL in these mice (see below).
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sPLA2 Transgenic Mice Exhibit Decreased Levels of
HDL-Cholesterol and Increased Levels of
LDL/VLDL-Cholesterol
To examine possible changes in the lipoprotein profile of the
sPLA2 transgenic mice on the high-fat diet, we
quantified plasma lipids and lipoproteins in transgenic and
nontransgenic littermates. Tables 1 and 2 show the results in males and females,
respectively. In addition, we examined elution profiles after
fractionation by gel filtration (Figure 5). Although total plasma
cholesterol and cholesteryl ester concentrations did not
differ significantly, plasma levels of free cholesterol
were approximately doubled in the transgenic mice compared with
controls (Tables 1 and 2). This difference was highly
significant and was not related to the type of diet. HDL
cholesterol levels were significantly reduced in the
transgenic mice compared with nontransgenic littermates on both the
chow diet and after 12 weeks on high-fat diet (Tables 1 and 2, Figure 5). In addition, there was a small but
significant increase in the levels of LDL/VLDL cholesterol
in the transgenic mice (Tables 1 and 2, Figure 5).
On the high-fat diet, total plasma cholesterol levels
tripled and the pro-atherogenic lipoprotein profile become more
accentuated in the transgenic mice compared with nontransgenic
littermates (Tables 1 and 2, Figure 5). Total
triglyceride concentrations did not differ between
transgenic and control mice on the chow diet.
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) and nontransgenic littermates (
) on chow or
atherogenic diets. Equal volumes of plasma pooled from 5 mice (400
µL) were injected onto 2 Superose 6 columns connected in series and
lipoproteins were separated by gel filtration as
described.
Paraoxonase Activity Is Reduced in Transgenic Mice
The changes in lipoprotein profiles in the
sPLA2 in transgenic mice are unlikely to entirely
explain the differences in atherogenesis (see Discussion). Because the
enzyme paraoxonase appears to be responsible, in part, for the
protective effects of HDL,19 20 21 22 we measured levels of the
enzyme in transgenic and nontransgenic mice. As shown in Figure 6A, paraoxonase activity was 3-fold
lower in pooled plasma from transgenic mice (34.5±4.1 U/mL) than in
controls (86.7±3.9 U/mL). FPLC fractions containing HDL of transgenic
mice also showed a marked decrease in activity compared with controls,
and paraoxonase in the transgenic mice was associated with smaller HDL
particles (Figure 6B).
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Discussion |
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Previous studies have suggested that sPLA2 may contribute to the development of atherosclerotic lesions,9 10 14 and we have examined this hypothesis directly using transgenic mice expressing human sPLA2. Consistent with previous studies,9 10 we observed abundant immunohistochemically localized sPLA2 in atherosclerotic lesions. The transgenic mice exhibited significantly increased lesions on a high-fat atherogenic diet as well as on a low-fat chow diet. The increase in lesion development appeared to result, in part, from decreased HDL and elevated LDL/VLDL levels. The levels of paraoxonase, an enzyme associated with HDL that protects against LDL oxidation and atherogenesis, were also substantially reduced in the sPLA2 transgenic mice compared with nontransgenic littermates. These points are discussed below.
The sPLA2 transgenic line used in these studies has previously been characterized with respect to sPLA2 expression in plasma and various tissue(s). The transgenic mice displayed severe hyperkeratosis and nearly complete loss of fur, but showed little or no inflammation in various tissues examined.8 To analyze lesion development, the transgene was transferred onto the genetic background of the C57BL/6J inbred strain. This strain has been studied extensively as a model for atherosclerosis because it is susceptible to the development of aortic fatty streak lesions when fed an atherogenic diet rich in saturated fat, cholesterol, and cholic acid.23 24 Studying the effects of the sPLA2 transgene on an inbred genetic background is also advantageous for reducing variability caused by genetic factors other than sPLA2. Moreover, the C57BL/6J strain exhibits an insertional point mutation causing a frameshift in exon 3 of the mouse sPLA2 gene, resulting in multiple transcripts that do not encode functional products.11 The genetic background of C57BL/6J, therefore, provided a very good contrast for the effects of the human transgene.
Immunohistochemical staining with a polyclonal antibody to human sPLA2 revealed the presence of the enzyme in atherosclerotic lesions of transgenic mice but not nontransgenic littermates. Previous studies have revealed the presence of sPLA2 in human atherosclerotic lesions.9 10 Liver sections of transgenic mice also displayed positive immunohistochemical sPLA2 staining and perivascular inflammatory infiltration, whereas sections from nontransgenic littermates were negative (data not shown). Human sPLA2 transgene expression was previously found to be highest in liver and to correlate well with serum activity.8
Our results demonstrate that the transgenic mice had significantly increased atherosclerotic lesions on an atherogenic diet as well as a low-fat diet. The latter results were surprising, given the relatively low levels of LDL and VLDL in the transgenic mice maintained on a chow diet. The lesions in sPLA2 transgenics fed a chow diet were similar in size and characteristic to those observed in apoA2 transgenic mice maintained on a chow diet.13 25 HDLs from apoA2 transgenic mice and from sPLA2 transgenic mice were similar in that both had reduced levels of paraoxonase and both failed to protect against LDL oxidation in cocultures of aortic endothelial cells and smooth muscle cell (discussed in the accompanying article, Reference 1818 ). The lesions in female mice, in both the transgenic and nontransgenic groups, were larger than lesions in male mice. This is a characteristic of both diet-induced lesions (Reference 2323 and references therein) and lesions in genetically engineered hypercholesterolemic mice (Reference 2424 and references therein).
Because previous studies have shown that plasma lipoproteins are substrates of sPLA2,14 we examined lipoprotein profiles of sPLA2 transgenic mice and nontransgenic littermates. Significant differences were observed between the groups on both the chow and the atherogenic diets. On both diets, sPLA2 transgenic mice exhibited significant elevations of LDL/VLDL-cholesterol and significant reductions of HDL-cholesterol, consistent with a pro-atherogenic change, and these correlated with the lesion sizes of the mice. Plasma-free fatty acids were not elevated in the transgenic mice, but this was not unexpected because free fatty acids are rapidly cleared from plasma. An unexpected result was the significantly increased levels of nonesterified cholesterol in the sPLA2 transgenic mice, which were nearly doubled compared with control mice both on chow and on atherogenic diets. The explanation for this is unclear but it may involve altered function of lecithin cholesterol acyl transferase (LCAT), an enzyme found in plasma that catalyzes the transfer of a fatty acid residue from the sn-2 position of lecithin to cholesterol to form cholesteryl ester, utilizing apoA1 as a cofactor. Conceivably, sPLA2 could alter LCAT function indirectly by changing HDL structure with respect to phospholipid composition or by inhibiting the interaction of apoA1 with LCAT on early discoidal HDL particles.26 Another interesting possibility is that LCAT may be inactivated by various reactive oxygen species. Bielicke et al27 have shown that oxidized LDL is a potent inhibitor of LCAT, and as shown in the accompanying studies,18 sPLA2 transgenic mice exhibit evidence of increased LDL oxidation. It is noteworthy that purified acute-phase serum amyloid A (SAA) can exchange for apoA1 on HDL particles and that the SAA can stimulate sPLA2 activity in vitro.28 SAA could contribute to our findings because SAA gene expression is markedly increased by the atherogenic diet in C57BL/6J mice.29 30
It seems unlikely that the observed changes in HDL and LDL/VLDL levels can entirely explain the dramatic effects of the sPLA2 transgene on atherosclerosis. Based on our previous studies with apoA2 transgenic mice13 25 and on in vitro studies of HDL,22 29 we hypothesized that there may be functional alterations of HDL as well. In particular, the capacity of HDL to inhibit LDL oxidation is attributed, in part, to the activity of the enzyme paraoxonase, which can act as an sn-2 ester hydrolyzing phospholipase, destroying biologically active phospholipid peroxides.20 Paraoxonase markedly inhibits cell-mediated LDL oxidation, and the inhibition of paraoxonase reduces HDL protection against LDL oxidation in the coculture model.20 22 We found that paraoxonase activity was significantly decreased in plasmas from the transgenic mice compared with controls. Serum paraoxonase is produced only in liver, and in serum it is tightly associated with apoA1. Displacement of apoA1 from HDL by SAA, as discussed above, also leads to a loss of paraoxonase activity.31 It is possible that the reduction in paraoxonase activity is because of reduced HDL levels. We have further examined the functional characteristics of plasma lipoproteins from the transgenic mice in the accompanying manuscript.18 It is also noteworthy that the uptake of LDL by macrophages is stimulated by PLA2 treatment.32
The relevance of these results for atherosclerosis in human populations is as yet unknown. However, it is interesting to speculate that sPLA2 could contribute to the increased atherosclerosis observed in various inflammatory diseases such as rheumatoid arthritis.33 Levels of sPLA2 in the circulation can rise many-fold during the acute phase response and in chronic inflammatory conditions such as arthritis and inflammatory bowel disease.6 Also, a variety of cells relevant to atherosclerosis, including neutrophils and macrophages, can secrete sPLA2 in response to inflammatory cytokines such as tumor necrosis factor and interleukin 1.34 35 The hypothesis that sPLA2 contributes to the inflammatory aspects of human atherogenesis warrants further investigation.
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Acknowledgments |
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This work was supported by National Institute of Health grants HL30568 (A.J.L., A.M.F.), AG10886 (F.C.d.B.), the Council for Tobacco Research (F.C.d.B.), and Veterans Administration Research Funds (F.C.d.B.). We thank Jay Lee for discussions. F. de Beer and A. Lusis contributed equally to this study.
Received January 12, 1998; accepted October 5, 1998.
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References |
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TopAbstractIntroductionMethodsResultsDiscussionReferences |
|---|
1. Kudo I, Murakami M, Hara S, Inoue K. Mammalian non-pancreatic phospholipases A2. Biochim Biophys Acta. 1993;1170:217–231.[Medline] [Order article via Infotrieve]
2.
Dennis EA. Diversity of group types, regulation, and
function of phospholipase A2. J Biol Chem. 1994;269:13057–13060.
3.
Tischfield JA. A reassessment of the low molecular
weight phospholipase A2 gene family in mammals. J Biol
Chem. 1997;272:17247–17250.
4. Sparrow CP, Parthasarathy S, Steinberg D. Enzymatic modification of low density lipoprotein by purified lipoxygenase plus phospholipase A2 mimics cell-mediated oxidative modification. J Lipid Res. 1988;29:745–753.[Abstract]
5.
Sakai M, Miyazaki A, Hakamata H, Sasaki T, Yui S,
Yamazaki M, Shichiri M, Horiuchi S. Lysophosphatidylcholine plays an
essential role in the mitogenic effect of oxidized low
density lipoprotein on murine macrophages. J Biol
Chem. 1994;269:31430–31435.
6.
Mangin EL Jr, Kugiyama K, Nguy JH, Kerns SA, Henry PD.
Effects of lysolipids and oxidatively modified low density lipoprotein
on endothelium-dependent relaxation of rabbit aorta.
Circ Res. 1993;72:161–166.
7. Kume N, Cybulsky MI, Gimbrone MA Jr. Lysophosphatidylcholine, a component of atherogenic lipoproteins, induces mononuclear leukocyte adhesion molecules in cultured human and rabbit arterial endothelial cells. J Clin Invest. 1992;90:1138–1144.
8. Grass DS, Felkner RH, Chiang M-Y, Wallace RE, Nevalainen TJ, Bennett CF, Swanson ME. Expression of human group II PLA2 in transgenic results in epidermal hyperplasia in the absence of inflammatory infiltrate. J Clin Invest. 1996;97:2233–2241.[Medline] [Order article via Infotrieve]
9.
Hurt-Camejo E, Andersen S, Standal R, Rosengren B,
Sartipy P, Stadberh E, Johansen B. Localization of non-pancreatic
secretory phospholipase A2 in normal and atherosclerotic arteries.
Arterioscler Thromb Vasc Biol. 1997;17:300–309.
10. Menschikowski M, Kasper M, Lattke P, Schiering A, Schiefer S, Stockinger H, Jaross W. Secretory group II phospholipase A2 in human atherosclerotic lesions. Atherosclerosis. 1995;118:173–181.[Medline] [Order article via Infotrieve]
11.
Kennedy BP, Payette P, Mudgett J, Vadas P, Pruzanski W,
Kwan M, Tang C, Rancourt DE, Cromlish WA. A natural disruption of the
secretory group II phospholipase A2 gene in inbred mouse strains.
J Biol Chem. 1995;270:22378–22385.
12.
Qiao J-H, Xie P-Z, Fishbein MC, Kreuzer J, Drake TA,
Demer LL, Lusis AJ. Pathology of the atheromatous
lesions in inbred and genetically engineered mice: genetic
determination of arterial calcification. Arterioscler
Thromb. 1994;14:1480–1497.
13.
Warden CH, Qiao JH, Castellani LW, Lusis AJ.
Atherosclerosis in transgenic mice overexpressing
apolipoprotein A-II. Science. 1993;261:469–472.
14. deBeer FC, deBeer MC, van der Westerhuyzen DR, Castellani LW, Lusis AJ, Swanson ME, Grass DS. Secretory non-pancreatic phospholipase A2:Influence on lipoprotein metabolism. J Lipid Res. 1997;38:2232–2239.[Abstract]
15. Lorenzen A, Kennedy SW. A fluorescence based protein assay for use with a microplate reader. Anal Biochem. 1993;214:346–348.[Medline] [Order article via Infotrieve]
16.
Lowry OH, Rosebrough MJ, Farr AL, Randall RJ. Protein
measurement with the folin phenol reagent. J Biol Chem. 1951;193:265–275.
17. Gan KN, Smolen A, Eckerson HW, La Du BN. Purification of human serum paraoxonase/arylesterase. Evidence for one esterase catalyzing both activities. Drug Metab Dispos. 1991;19:100–106.[Abstract]
18.
Leitinger N, Watson AD, Hama S, Ivandic B, Qiao JH,
Huber J, Faull KF, Grass DS, Navab M, Fogelman AM, de Beer FC, Lusis
AJ, Berliner JA. Role of the group II secretory
PLA2 in atherosclerosis: 2.
Potential involvement of biologically active oxidized phospholipids.
Arterioscler Thromb Vasc Biol. 1999;19:1291–1298.
19. Mackness MI, Arrol S, Durrington PN. Paraoxonase prevents accumulation of lipoperoxides in low-density lipoprotein. FEBS Lett. 1991;286:152–154.[Medline] [Order article via Infotrieve]
20. Watson AD, Berliner JA, Hama SY, La Du BN, Faull KF, Fogelman AM, Navab M. Protective effect of high density lipoprotein associated paraoxonase. Inhibition of the biological activity of minimally oxidized low density lipoprotein. J Clin Invest. 1995;96:2882–2891.
21. Parthasarathy, Barnett J, Fong LG. High-density lipoprotein inhibits the oxidative modification of low-density lipoprotein. Biochim Biophys Acta. 1990;1044:275–283.[Medline] [Order article via Infotrieve]
22. Shih DM, Gu L, Hama S, Xia Y, Navab M, Fogelman AM, Lusis AJ. Genetic-dietary regulation of serum paraoxonase expression and its role in atherogenesis in a mouse model. J Clin Invest. 1996;97:1630–1639.[Medline] [Order article via Infotrieve]
23. Paigen B, Morrow A, Holmes PA, Mitchell D, Williams RA. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis. 1987;68:231–240.[Medline] [Order article via Infotrieve]
24.
Weng W, Breslow JL. Dramatically decreased high density
lipoprotein cholesterol, increased remnant clearance, and
insulin hypersensitivity in apolipoprotein A-II knockout mice suggest a
complex role for apolipoprotein AII in atherosclerosis
susceptibility. Proc Natl Acad Sci U S A. 1996;93:14788–14794.
25. Castellani LW, Navab M, van Lenten BJ, Hama S, Hedrick C, Fogelman AM, Lusis AJ. Apolipoprotein AII overexpression converts the anti-inflammatory HDL to pro-inflammatory particles. J Clin Invest. 1997;100:464–474.[Medline] [Order article via Infotrieve]
26. Fielding CJ, Fielding PE. The molecular physiology of reverse cholesterol transport. J Lipid Res. 1995;36:211–228.[Abstract]
27. Bielicke JK, Forte TM, McCall MR. Minimally oxidized LDL is a potent inhibitor of lecithin:cholesterol acyltransferase activity. J Lipid Res. 1996;37:1012–1021.[Abstract]
28. Pruzanski W, de Beer FC, de Beer MC, Stefanski E, Vadas P. Serum amyloid A protein enhances the activity of secretory non-pancreatic phospholipase A2. Biochem J. 1995;309:461–464.
29. Liao F, Andalibi A, deBeer FC, Fogelman AM, Lusis AJ. Genetic control of inflammatory gene induction and NF-kB-like transcription factor activation in response to an atherogenic diet in mice. J Clin Invest. 1993;91:2572–2579.
30. Liao F, Andalibi A, Qiao J-H, Allayee H, Fogelman AM, Lusis AJ. Genetic evidence for a common pathway mediating oxidative stress, inflammatory gene induction, and aortic fatty streak formation in mice. J Clin Invest. 1994;94:877–884.
31. Van Lenten BJ, Hama SY, deBeer FC, Stafforini DM, McIntyre TM, Prescott SM, La Du BN, Fogelman AM, Navab M. Anti-inflammatory HDL becomes pro-inflammatory during the acute phase response. Loss of protective effect of HDL against LDL oxidation in aortic wall cell co-cultures. J Clin Invest. 1995;96:2758–2767.
32. Menschikowski M, Lattke P, Bergmann S, Jaross W. Exposure of macrophages to PLA2-modified lipoproteins leads to cellular lipid accumulations. Anal Cell Pathol. 1995;9:113–121.[Medline] [Order article via Infotrieve]
33. Wolfe F, Mitchell DM, Sibley JT, Fries JF, Bloch DA, Williams CA, Spitz PW, Haga M, Kleinheksel S, Cathey MA. The mortality of rheumatoid arthritis. Arthritis Rheum. 1994;37:481–494.[Medline] [Order article via Infotrieve]
34. Rosenthal MD, Gordon MN, Buescher ES, Slusser JH, Harris LK, Franson RC. Human neutrophils store type II 14-kDa phospholipase A2 in granules and secrete active enzyme in response to soluble stimuli. Biochem Biophys Res Commun. 1995;208:650–656.[Medline] [Order article via Infotrieve]
35. Arbibe L, Vial D, Rosinski-Chupin I, Havet N, Huerre M, Vargaftig BB, Touqui L. Endotoxin induces expression of type II phospholipase A2 in macrophages during acute lung injury in guinea pigs: involvement of TNF-alpha in lipopolysaccharide-induced type II phospholipase A2 synthesis. J Immunol. 1997;159:391–400.[Abstract]
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 H. Sato, R. Kato, Y. Isogai, G.-i. Saka, M. Ohtsuki, Y. Taketomi, K. Yamamoto, K. Tsutsumi, J. Yamada, S. Masuda, et al. Analyses of Group III Secreted Phospholipase A2 Transgenic Mice Reveal Potential Participation of This Enzyme in Plasma Lipoprotein Modification, Macrophage Foam Cell Formation, and Atherosclerosis J. Biol. Chem., November 28, 2008; 283(48): 33483 - 33497. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Divchev, C. Grothusen, M. Luchtefeld, M. Thoenes, F. Onono, R. Koch, H. Drexler, and B. Schieffer Impact of a combined treatment of angiotensin II type 1 receptor blockade and 3-hydroxy-3-methyl-glutaryl-CoA-reductase inhibition on secretory phospholipase A2-type IIA and low density lipoprotein oxidation in patients with coronary artery disease Eur. Heart J., August 2, 2008; 29(16): 1956 - 1965. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. J. F. Tietge, N. Nijstad, R. Havinga, J. F. W. Baller, F. H. van der Sluijs, V. W. Bloks, T. Gautier, and F. Kuipers Secretory phospholipase A2 increases SR-BI-mediated selective uptake from HDL but not biliary cholesterol secretion J. Lipid Res., March 1, 2008; 49(3): 563 - 571. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Ravaux, C. Denoyelle, C. Monne, I. Limon, M. Raymondjean, and K. El Hadri Inhibition of Interleukin-1{beta}-Induced Group IIA Secretory Phospholipase A2 Expression by Peroxisome Proliferator-Activated Receptors (PPARs) in Rat Vascular Smooth Muscle Cells: Cooperation between PPAR{beta} and the Proto-Oncogene BCL-6 Mol. Cell. Biol., December 1, 2007; 27(23): 8374 - 8387. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. T.E. Wootton, N. L. Arora, F. Drenos, S. R. Thompson, J. A. Cooper, J. W. Stephens, S. J. Hurel, E. Hurt-Camejo, O. Wiklund, S. E. Humphries, et al. Tagging SNP haplotype analysis of the secretory PLA2-V gene, PLA2G5, shows strong association with LDL and oxLDL levels, suggesting functional distinction from sPLA2-IIA: results from the UDACS study Hum. Mol. Genet., June 15, 2007; 16(12): 1437 - 1444. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Mallat, J. Benessiano, T. Simon, S. Ederhy, C. Sebella-Arguelles, A. Cohen, V. Huart, N. J. Wareham, R. Luben, K.-T. Khaw, et al. Circulating Secretory Phospholipase A2 Activity and Risk of Incident Coronary Events in Healthy Men and Women: The EPIC-NORFOLK Study Arterioscler. Thromb. Vasc. Biol., May 1, 2007; 27(5): 1177 - 1183. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. Keshav Paneth cells: leukocyte-like mediators of innate immunity in the intestine J. Leukoc. Biol., September 1, 2006; 80(3): 500 - 508. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
F. C. de Beer and N. R. Webb Inflammation and atherosclerosis: Group IIa and Group V sPLA2 are not redundant. Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1421 - 1422. [Full Text] [PDF]
|
|
|
|
|
|
B. Rosengren, H. Peilot, M. Umaerus, A.-C. Jonsson-Rylander, L. Mattsson-Hulten, C. Hallberg, P. Cronet, M. Rodriguez-Lee, and E. Hurt-Camejo Secretory Phospholipase A2 Group V: Lesion Distribution, Activation by Arterial Proteoglycans, and Induction in Aorta by a Western Diet Arterioscler. Thromb. Vasc. Biol., July 1, 2006; 26(7): 1579 - 1585. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Dronadula, F. Rizvi, E. Blaskova, Q. Li, and G. N. Rao Involvement of cAMP-response element binding protein-1 in arachidonic acid-induced vascular smooth muscle cell motility J. Lipid Res., April 1, 2006; 47(4): 767 - 777. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. T.E. Wootton, F. Drenos, J. A. Cooper, S. R. Thompson, J. W. Stephens, E. Hurt-Camejo, O. Wiklund, S. E. Humphries, and P. J. Talmud Tagging-SNP haplotype analysis of the secretory PLA2IIa gene PLA2G2A shows strong association with serum levels of sPLA2IIa: results from the UDACS study Hum. Mol. Genet., January 15, 2006; 15(2): 355 - 361. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 Z. Mallat, Ph. G. Steg, J. Benessiano, M.-L. Tanguy, K. A. Fox, J.-P. Collet, O. H. Dabbous, P. Henry, K. F. Carruthers, A. Dauphin, et al. Circulating Secretory Phospholipase A2 Activity Predicts Recurrent Events in Patients With Severe Acute Coronary Syndromes J. Am. Coll. Cardiol., October 4, 2005; 46(7): 1249 - 1257. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. J. F. Tietge, D. Pratico, T. Ding, C. D. Funk, R. B. Hildebrand, T. Van Berkel, and M. Van Eck Macrophage-specific expression of group IIA sPLA2 results in accelerated atherogenesis by increasing oxidative stress J. Lipid Res., August 1, 2005; 46(8): 1604 - 1614. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
B. W. Parks, G. P. Gambill, A. J. Lusis, and J. H. S. Kabarowski Loss of G2A promotes macrophage accumulation in atherosclerotic lesions of low density lipoprotein receptor-deficient mice J. Lipid Res., July 1, 2005; 46(7): 1405 - 1415. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Jaulmes, B. Janvier, M. Andreani, and M. Raymondjean Autocrine and Paracrine Transcriptional Regulation of Type IIA Secretory Phospholipase A2 Gene in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., June 1, 2005; 25(6): 1161 - 1167. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. P.J. de Winther, E. Kanters, G. Kraal, and M. H. Hofker Nuclear Factor {kappa}B Signaling in Atherogenesis Arterioscler. Thromb. Vasc. Biol., May 1, 2005; 25(5): 904 - 914. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. M. Boekholdt, T. T. Keller, N. J. Wareham, R. Luben, S. A. Bingham, N. E. Day, M. S. Sandhu, J. W. Jukema, J. J.P. Kastelein, C. E. Hack, et al. Serum Levels of Type II Secretory Phospholipase A2 and the Risk of Future Coronary Artery Disease in Apparently Healthy Men and Women: The EPIC-Norfolk Prospective Population Study Arterioscler. Thromb. Vasc. Biol., April 1, 2005; 25(4): 839 - 846. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
A. Chait, C. Y. Han, J. F. Oram, and J. W. Heinecke Thematic review series: The Immune System and Atherogenesis. Lipoprotein-associated inflammatory proteins: markers or mediators of cardiovascular disease? J. Lipid Res., March 1, 2005; 46(3): 389 - 403. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. A. I. Ghesquiere, M. J. J. Gijbels, M. Anthonsen, P. J. J. van Gorp, I. van der Made, B. Johansen, M. H. Hofker, and M. P. J. de Winther Macrophage-specific overexpression of group IIa sPLA2 increases atherosclerosis and enhances collagen deposition J. Lipid Res., February 1, 2005; 46(2): 201 - 210. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. D. Curb, R. D. Abbott, B. L. Rodriguez, K. H. Masaki, R. Chen, J. S. Popper, H. Petrovitch, G. W. Ross, I. J. Schatz, G. C. Belleau, et al. High Density Lipoprotein Cholesterol and the Risk of Stroke in Elderly Men: The Honolulu Heart Program Am. J. Epidemiol., July 15, 2004; 160(2): 150 - 157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Khovidhunkit, M.-S. Kim, R. A. Memon, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld Thematic review series: The Pathogenesis of Atherosclerosis. Effects of infection and inflammation on lipid and lipoprotein metabolism mechanisms and consequences to the host J. Lipid Res., July 1, 2004; 45(7): 1169 - 1196. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. R. Wooton-Kee, B. B. Boyanovsky, M. S. Nasser, W. J.S. de Villiers, and N. R. Webb Group V sPLA2 Hydrolysis of Low-Density Lipoprotein Results in Spontaneous Particle Aggregation and Promotes Macrophage Foam Cell Formation Arterioscler. Thromb. Vasc. Biol., April 1, 2004; 24(4): 762 - 767. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 K. Winkler, C. Abletshauser, I. Friedrich, M. M. Hoffmann, H. Wieland, and W. Marz Fluvastatin Slow-Release Lowers Platelet-Activating Factor Acetyl Hydrolase Activity: A Placebo-Controlled Trial in Patients with Type 2 Diabetes J. Clin. Endocrinol. Metab., March 1, 2004; 89(3): 1153 - 1159. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 P. E. Szmitko, C.-H. Wang, R. D. Weisel, G. A. Jeffries, T. J. Anderson, and S. Verma Biomarkers of Vascular Disease Linking Inflammation to Endothelial Activation: Part II Circulation, October 28, 2003; 108(17): 2041 - 2048. [Full Text] [PDF]
|
|
|
|
 |
|
 H. W.M Niessen, P. A.J Krijnen, C. A Visser, C. J.L.M Meijer, and C Erik Hack Type II secretory phospholipase A2 in cardiovascular disease: a mediator in atherosclerosis and ischemic damage to cardiomyocytes? Cardiovasc Res, October 15, 2003; 60(1): 68 - 77. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 B. OSTERUD and E. BJORKLID Role of Monocytes in Atherogenesis Physiol Rev, October 1, 2003; 83(4): 1069 - 1112. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. R. Webb, M. A. Bostrom, S. J. Szilvassy, D. R. van der Westhuyzen, A. Daugherty, and F. C. de Beer Macrophage-Expressed Group IIA Secretory Phospholipase A2 Increases Atherosclerotic Lesion Formation in LDL Receptor-Deficient Mice Arterioscler. Thromb. Vasc. Biol., February 1, 2003; 23(2): 263 - 268. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
D. Y. Hui and P. N. Howles Carboxyl ester lipase: structure-function relationship and physiological role in lipoprotein metabolism and atherosclerosis J. Lipid Res., December 1, 2002; 43(12): 2017 - 2030. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 L. Fuentes, M. Hernandez, F. J. Fernandez-Aviles, M. S. Crespo, and M. L. Nieto Cooperation Between Secretory Phospholipase A2 and TNF-Receptor Superfamily Signaling: Implications for the Inflammatory Response in Atherogenesis Circ. Res., October 18, 2002; 91(8): 681 - 688. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Barter Effects of Inflammation on High-Density Lipoproteins Arterioscler. Thromb. Vasc. Biol., July 1, 2002; 22(7): 1062 - 1063. [Full Text] [PDF]
|
|
|
|
|
|
U. J.F. Tietge, C. Maugeais, S. Lund-Katz, D. Grass, F. C. deBeer, and D. J. Rader Human Secretory Phospholipase A2 Mediates Decreased Plasma Levels of HDL Cholesterol and ApoA-I in Response to Inflammation in Human ApoA-I Transgenic Mice Arterioscler. Thromb. Vasc. Biol., July 1, 2002; 22(7): 1213 - 1218. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 A. MERTENS and P. HOLVOET Oxidized LDL and HDL: antagonists in atherothrombosis FASEB J, October 1, 2001; 15(12): 2073 - 2084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. Hurt-Camejo, G. Camejo, H. Peilot, K. Oorni, and P. Kovanen Phospholipase A2 in Vascular Disease Circ. Res., August 17, 2001; 89(4): 298 - 304. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. L. Welch, S. Bretschger, N. Latib, M. Bezouevski, Y. Guo, N. Pleskac, C.-P. Liang, C. Barlow, H. Dansky, J. L. Breslow, et al. Localization of atherosclerosis susceptibility loci to chromosomes 4 and 6 using the Ldlr knockout mouse model PNAS, July 3, 2001; 98(14): 7946 - 7951. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. R. Guyton Phospholipid Hydrolytic Enzymes in a 'Cesspool' of Arterial Intimal Lipoproteins : A Mechanism for Atherogenic Lipid Accumulation Arterioscler. Thromb. Vasc. Biol., June 1, 2001; 21(6): 884 - 886. [Full Text] [PDF]
|
|
|
|
|
|
C. Couturier, V. Antonio, A. Brouillet, G. Bereziat, M. Raymondjean, and M. Andreani Protein Kinase A-Dependent Stimulation of Rat Type II Secreted Phospholipase A2 Gene Transcription Involves C/EBP-{beta} and -{{delta}} in Vascular Smooth Muscle Cells Arterioscler. Thromb. Vasc. Biol., December 1, 2000; 20(12): 2559 - 2565. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
J. W. Knowles and N. Maeda Genetic Modifiers of Atherosclerosis in Mice Arterioscler. Thromb. Vasc. Biol., November 1, 2000; 20(11): 2336 - 2345. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 C. J. Packard, D. S.J. O'Reilly, M. J. Caslake, A. D. McMahon, I. Ford, J. Cooney, C. H. Macphee, K. E. Suckling, M. Krishna, F. E. Wilkinson, et al. Lipoprotein-Associated Phospholipase A2 as an Independent Predictor of Coronary Heart Disease N. Engl. J. Med., October 19, 2000; 343(16): 1148 - 1155. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
W. Pruzanski, E. Stefanski, F. C. de Beer, M. C. de Beer, A. Ravandi, and A. Kuksis Comparative analysis of lipid composition of normal and acute-phase high density lipoproteins J. Lipid Res., July 1, 2000; 41(7): 1035 - 1047. [Abstract] [Full Text]
|
|
|
|
|
|
K. Kugiyama, Y. Ota, H. Kawano, H. Soejima, H. Ogawa, S. Sugiyama, H. Doi, and H. Yasue Increase in plasma levels of secretory type II phospholipase A2 in patients with coronary spastic angina Cardiovasc Res, July 1, 2000; 47(1): 159 - 165. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Mietus-Snyder, M. S. Gowri, and R. E. Pitas Class A Scavenger Receptor Up-regulation in Smooth Muscle Cells by Oxidized Low Density Lipoprotein. ENHANCEMENT BY CALCIUM FLUX AND CONCURRENT CYCLOOXYGENASE-2 UP-REGULATION J. Biol. Chem., June 2, 2000; 275(23): 17661 - 17670. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
U. J. F. Tietge, C. Maugeais, W. Cain, D. Grass, J. M. Glick, F. C. de Beer, and D. J. Rader Overexpression of Secretory Phospholipase A2 Causes Rapid Catabolism and Altered Tissue Uptake of High Density Lipoprotein Cholesteryl Ester and Apolipoprotein A-I J. Biol. Chem., March 31, 2000; 275(14): 10077 - 10084. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. T. Kovanen and M. O. Pentikainen Secretory Group II Phospholipase A2 : A Newly Recognized Acute-Phase Reactant With a Role in Atherogenesis Circ. Res., March 31, 2000; 86(6): 610 - 612. [Full Text] [PDF]
|
|
|
|
|
|
P. Sartipy, B. Johansen, K. Gasvik, and E. Hurt-Camejo Molecular Basis for the Association of Group IIA Phospholipase A2 and Decorin in Human Atherosclerotic Lesions Circ. Res., March 31, 2000; 86(6): 707 - 714. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
S. Parthasarathy, N. Santanam, S. Ramachandran, and O. Meilhac Oxidants and antioxidants in atherogenesis: an appraisal J. Lipid Res., December 1, 1999; 40(12): 2143 - 2157. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
P. Sartipy, G. Camejo, L. Svensson, and E. Hurt-Camejo Phospholipase A2 Modification of Low Density Lipoproteins Forms Small High Density Particles with Increased Affinity for Proteoglycans and Glycosaminoglycans J. Biol. Chem., September 3, 1999; 274(36): 25913 - 25920. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
N. Leitinger, A. D. Watson, S. Y. Hama, B. Ivandic, J.-H. Qiao, J. Huber, K. F. Faull, D. S. Grass, M. Navab, A. M. Fogelman, et al. Role of Group II Secretory Phospholipase A2 in Atherosclerosis : 2. Potential Involvement of Biologically Active Oxidized Phospholipids Arterioscler. Thromb. Vasc. Biol., May 1, 1999; 19(5): 1291 - 1298. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
H. Peilot, B. Rosengren, G. Bondjers, and E. Hurt-Camejo Interferon-gamma Induces Secretory Group IIA Phospholipase A2 in Human Arterial Smooth Muscle Cells. INVOLVEMENT OF CELL DIFFERENTIATION, STAT-3 ACTIVATION, AND MODULATION BY OTHER CYTOKINES J. Biol. Chem., July 21, 2000; 275(30): 22895 - 22904. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. Murakami, R. S. Koduri, A. Enomoto, S. Shimbara, M. Seki, K. Yoshihara, A. Singer, E. Valentin, F. Ghomashchi, G. Lambeau, et al. Distinct Arachidonate-releasing Functions of Mammalian Secreted Phospholipase A2s in Human Embryonic Kidney 293 and Rat Mastocytoma RBL-2H3 Cells through Heparan Sulfate Shuttling and External Plasma Membrane Mechanisms J. Biol. Chem., March 23, 2001; 276(13): 10083 - 10096. [Abstract] [Full Text] [PDF]
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