Atherosclerosis and Lipoproteins |
From the Departments of Medicine (R.A.M., M.N., A.H.M., K.R.F., C.G.), Surgery (I.S.) and Dermatology (W.M.H., Y.U.), University of California San Francisco, Calif, and Metabolism Section (R.A.M., M.N., A.H.M., K.R.F., C.G.), Medical Service, Department of Veterans Affairs Medical Center, San Francisco, Calif.
Correspondence to Riaz A. Memon, PhD, Department of Veterans Affairs Medical Center, Metabolism Section (111F), 4150 Clement St, San Francisco, CA 94121. E-mail rmemon{at}itsa.ucsf.edu
| Abstract |
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Key Words: lipoproteins atherosclerosis infection inflammation
| Introduction |
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APR represents a complex reaction of the host that is characterized by changes in serum levels of specific proteins such as C-reactive protein and serum amyloid A.9 APR is accompanied by alterations in lipid metabolism that include increased serum triglycerides and decreased HDL levels.10 These changes also can be produced by administration of endotoxin (lipopolysaccharide [LPS]), a well-characterized inducer of APR. LPS rapidly increases serum triglyceride levels by stimulating hepatic VLDL production and by decreasing triglyceride clearance.11 In rodents, LPS increases serum cholesterol levels by increasing LDL,12 whereas in primates, LDL levels decrease during infection but an increase occurs in small, dense LDL.13 Finally, LPS decreases HDL levels in both rodents and primates.11 12 13 The increase in triglycerides and small, dense LDL and the decrease in HDL are proatherogenic.
Oxidative modification of lipoproteins plays a central role in the pathogenesis of atherosclerosis.14 15 Oxidized LDL exerts several proatherogenic effects, which include increased synthesis and secretion of adhesion molecules, monocyte chemotaxis and adhesion, cytotoxicity to endothelial cells, enhanced foam cell formation, and increased smooth muscle cell proliferation.14 15 Moreover, lipoproteins with oxidative damage and lipid peroxidation products have been detected in atherosclerotic lesions.14 15 Finally, several structurally unrelated antioxidants slow the progression of atherosclerosis14 15 ; whereas oxidized lipids in the diet enhance atherosclerosis.16 17 Although these studies support a role for oxidized lipoproteins in atherogenesis, the mechanisms by which lipoproteins are oxidized in vivo are unknown. Moreover, the pathogenic stimuli that induce lipoprotein oxidation in vivo have not been identified. Under normal circumstances, circulating LDL is protected from oxidative stress by HDL-associated enzymes, particularly paraoxonase, which destroys biologically active oxidized phospholipids.18
Van Lenten et al19 have shown that serum paraoxonase activity is decreased in rabbits after croton oil administration, and paraoxonase depleted HDL is unable to protect LDL from oxidation in vitro. We have recently reported that LPS, tumor necrosis factor, and interleukin-1 decrease serum paraoxonase activity and hepatic paraoxonase mRNA levels in Syrian hamsters in vivo,20 which suggests that the decrease in paraoxonase is a feature of APR. Because reactive oxygen is generated as part of host defense9 and paraoxonase protects LDL from oxidative stress, we postulated that APR may increase LDL oxidation in vivo. We have now examined this hypothesis in 3 distinct models of infection and inflammation, which are produced by administration of LPS (acute systemic infection), zymosan (acute noninfectious systemic inflammation), and turpentine (acute localized sterile inflammation). Each of these stimuli is a well-characterized inducer of APR.11 21 22
| Methods |
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Animal Procedures
Male Syrian hamsters (
140 to 160 g) were purchased from
Charles River Laboratories (Wilmington, Mass). We chose Syrian hamsters
because compared with that in mice and rats, lipoprotein
metabolism in Syrian hamsters closely resembles that in
humans. For example, Syrian hamsters have substantial plasma LDL, and
the LDL levels change in response to dietary manipulations in a fashion
similar to humans.23 Animals were kept on a normal light
cycle and provided with rodent chow and water ad libitum. The Syrian
hamsters were injected either with LPS (0.1 to 100 µg per 100 g
body weight [BW] IP), zymosan (10 mg per 100 g BW IP),
turpentine (0.5 mL/100 g BW SC), or saline. Subsequently, food was
withdrawn from both control and treated animals because APR induces
anorexia.11 22 Animals were studied between 4 and 48 hours
after LPS treatment and 24 hours after zymosan or turpentine. Doses of
LPS used here are much lower than the doses that induce lethality in
rodents (LD50,
5 mg per 100 g BW) but
have significant effects on lipoprotein metabolism in
Syrian hamsters.12 Similarly, doses of zymosan and
turpentine used have been shown to induce APR.21 22
Isolation of Lipoproteins and Measurement of Lipoprotein
Oxidation
At indicated times after LPS, turpentine, or zymosan treatment,
animals were anesthetized with isoflurane and their blood was
obtained. Samples were processed immediately. Lipoproteins were
isolated by use of density-gradient
ultracentrifugation.24 Butylated
hydroxytoluene (final concentration, 5 µmol/L) was added to all
lipoprotein fractions to prevent further oxidation. Lipid peroxidation
products in serum and lipoprotein fractions were measured by use of
several methods. Conjugated diene content was measured by the
second-derivative UV spectroscopy method25 as described
earlier.26 Lipid peroxide levels were measured by the
method of Ohishi et al.27 Lipid peroxide decomposition
products, which consist of a variety of aldehydes, were measured as
thiobarbituric acidreactive substances (TBARS) as described by Morel
et al.28 Lysophosphatidylcholine (LPC) content in
lipoprotein fractions was measured by the method of Quinn et
al.29 The LPC band on silica-gel plates was identified by
comigration with standard, scraped, and assayed for phosphorus content
as described.30
LDL Oxidation Ex Vivo
Susceptibility of LDL to ex vivo oxidation was determined by
continuous monitoring (every 15 minutes for 4 hours at 37°C) of
conjugated diene production31 as described
previously.26 Susceptibility to oxidation is expressed as
the "lag time" and is determined from an intercept of lines drawn
through the linear portion of lag and propagation phases for each
sample. At the end of incubation, the levels of TBARS formed were also
measured.28
Statistics
Results are presented as mean±SEM. Statistical
significance between 2 groups was determined by use of Students
t test. Comparison among >2 groups was done by ANOVA with
statistical significance calculated with Bonferronis
multiple-comparison test.
| Results |
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48 hours (2-fold increase compared with controls). LPS had no
significant effect on conjugated dienes at earlier time points. LPS
also produced a 62% and 83% increase in serum TBARS after 24 and 48
hours of administration, respectively (Figure 1B
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To determine whether the increase in lipid oxidation products is
limited to LPS or is seen with other APR inducers, we examined the
effect of zymosan (a model for acute systemic inflammation) and
turpentine (a model for acute localized inflammation) on
serum-conjugated dienes and TBARS. Because the baseline levels of
conjugated dienes and TBARS may vary between animal groups depending on
their antioxidant status, each experimental group was compared with its
own control group from the same set of animals. Zymosan 10 mg per
100 g BW IP produced a 2.2 fold increase in serum-conjugated
dienes, whereas turpentine 0.5 mL per 100 g BW SC increased
conjugated dienes by 52% (Figure 3A
).
Similarly, zymosan and turpentine increased serum TBARS by 61% and
72%, respectively (Figure 3B
), which demonstrated that serum
lipid peroxidation products are increased in several distinct
models of infection and inflammation.
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Infection and Inflammation Increase Lipoprotein Oxidation In
Vivo
We next examined the effect of treatment with LPS and zymosan on
conjugated dienes, lipid hydroperoxides, and TBARS in lipoprotein
fractions. TBARS were not detectable in any fraction. Basal levels of
conjugated dienes and lipid hydroperoxides were low in lipoprotein
fractions from saline-treated animals. LPS produced a 7-fold increase
in conjugated diene content in the LDL fraction when presented
as nanomoles per milligram LDL protein (Figure 4A
). Similarly, zymosan produced a
4.8-fold increase in conjugated diene content (nanomoles per
milligram protein) in the LDL fraction (Figure 4A
). Levels of
conjugated dienes in the LDL fraction from LPS-treated animals were
3.9-fold higher when expressed as nanomoles per milligram LDL
triglycerides and 8.1-fold higher when presented as
nanomoles per milligram LDL cholesterol. Similarly,
levels of conjugated dienes in the LDL fraction from zymosan-treated
animals were 6.1-fold higher when expressed as nanomoles per
milligram LDL triglycerides and 6.3-fold higher when
presented as nanomoles per milligram LDL
cholesterol. No significant effect of LPS or zymosan was
seen on conjugated diene content of VLDL and HDL fractions when
adjusted for protein, triglyceride, or
cholesterol content (data not shown).
|
Both LPS and zymosan increased lipid hydroperoxides (nanomoles per
milligram protein) in the LDL fraction by 4.3-fold and 2.9-fold,
respectively (Figure 4B
). Increases in hydroperoxides were also
significant when expressed as nanomoles per milligram LDL
triglycerides (3.9-fold for LPS and 3.8-fold for zymosan)
or as nanomoles per milligram LDL cholesterol (5.5-fold
for LPS and 5.1-fold for zymosan). Neither LPS nor zymosan altered
hydroperoxide levels in VLDL or HDL fraction when adjusted for protein,
triglyceride, or cholesterol content (data not
shown).
Susceptibility of LDL to Ex Vivo Oxidation
We next determined whether LDL oxidized in vivo during the host
response to infection or inflammation is more susceptible to further
oxidation ex vivo. To address this question, we isolated LDL from
hamsters treated with LPS (100 µg per 100 g BW; 24-hour
treatment) or saline and examined its susceptibility to ex vivo
oxidation with copper sulfate (1.67 µmol/L) by monitoring the
formation of conjugated dienes every 15 minutes for 4 hours at 37°C.
LDL obtained from LPS-treated animals was significantly more
susceptible to ex vivo oxidation at every time point (Figure 5
). LDL obtained from LPS-treated
hamsters had a shorter lag phase followed by a propagation phase that
reached plateau by 4 hours, whereas LDL obtained from controls had a
longer lag phase, and in some samples the propagation phase was not
generated after 4 hours. Mean lag time for the onset of oxidation was
significantly shorter for the LDL obtained from LPS-treated hamsters
(control 92.5±10.3 minutes versus LPS 31.2±4.7 minutes;
P<0.001). Moreover, at the end of the 4-hour reaction, a
3.2-fold increase occurred in TBARS in the incubation medium that
contained LDL isolated from LPS-treated animals (control 17±1.6 versus
LPS 54±4.5 malondialdehyde equivalents per milligram LDL protein;
P<0.001). These results indicate that the host response to
infection produces LDL that not only contains more oxidized lipids, but
is also more susceptible to further oxidation.
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LPS Increases LPC Content in LDL
Oxidative modification of LDL is associated with increased
formation of LPC, a product of phosphatidylcholine hydrolysis, and
this reaction is primarily mediated by plasma-activating
factoracetylhydrolase (PAF-AH).32 We have recently shown
that LPS increases plasma PAF-AH activity in Syrian
hamsters.33 We therefore postulated that LPS should
increase LPC content in the LDL fraction. As shown in Figure 6
, basal levels of LPC are low in the LDL
fraction and LPS treatment produces a 17-fold increase in LPC content
in LDL. No significant effect of LPS existed on LPC content in VLDL or
HDL (data not shown).
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| Discussion |
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-tocopherol and ascorbate.35 Thus, it is
unclear whether oxidized lipoproteins originate in the
arterial wall or are produced in the circulation and then
enter the intimal space. The present study demonstrates that systemic oxidation of lipoprotein particles occurs as part of the host response to infection and inflammation. These conclusions are based on several observations. First, both serum-conjugated dienes (which measure the initial phase of lipid peroxidation) and TBARS (which measure the degradation phase of lipid peroxidation) are increased in Syrian hamsters after LPS administration. This increase in serum-oxidized lipids is a dose-dependent effect seen 24 hours after LPS administration and is sustained for at least 48 hours. The LPS-induced increase in serum triglycerides occurs within 90 minutes,11 whereas changes in oxidized lipids are not seen until 24 hours after LPS treatment, which indicates that increase in oxidized lipids in serum is not simply a result of increased availability of fatty acid substrate. Second, serum-conjugated dienes and TBARS are increased in animals treated with either zymosan or turpentine, which produces systemic or localized inflammation, respectively.21 22 Third, conjugated dienes and lipid hydroperoxides are markedly increased in circulating LDL from animals treated with either LPS or zymosan, which indicates that LDL oxidation occurs in 2 distinct models of acute infection and inflammation. The significant increase in conjugated dienes and lipid hydroperoxides in LDL persists when expressed as nanomoles per milligram protein, triglycerides, or cholesterol, which suggests that increased oxidation of LDL is not merely a result of changes in the composition of LDL during APR.12 More-dramatic changes in the composition of VLDL and HDL occur during APR.12 However, no change occurs in the oxidation status of these fractions when adjusted for triglyceride, cholesterol, or protein content. Fourth, LPC content, a marker for oxidative modification of LDL, is increased in circulating LDL after LPS treatment, which indicates that lipoprotein phospholipids are oxidized in vivo during APR. Fifth, LDL isolated from LPS-treated animals is more susceptible to ex vivo oxidation, which suggests that acute-phase LDL may be more susceptible to further oxidation in the vessel wall. Together, these results indicate that the host response to infection and inflammation is a potent stimulus for producing oxidation of serum lipids, including circulating LDL.
Several mechanisms could contribute to increased LDL oxidation during APR. Paraoxonase is a HDL-associated enzyme that protects LDL from oxidative stress by destroying biologically active phospholipids.18 Van Lenten et al19 have reported a decrease in serum paraoxonase activity both in rabbits after croton oil was administered and in humans postoperatively.19 We have recently shown that LPS, tumor necrosis factor, and interleukin-1 decrease hepatic paraoxonase mRNA expression and serum paraoxonase activity in Syrian hamsters.20 Castellani et al36 have shown that depletion of paraoxonase results in the loss of the antioxidant function of HDL, and addition of paraoxonase to HDL restores the protective function of HDL. Moreover, Aviram et al37 also reported that purified paraoxonase is a potent inhibitor of LDL and HDL oxidation in vitro. Finally, lipoproteins isolated from paraoxonase knockout mice are more susceptible to oxidation than lipoproteins isolated from their wild-type littermates,38 and paraoxonase knockout mice on a high fathigh cholesterol diet are more susceptible to atherosclerosis.38 These results suggest that paraoxonase may protect LDL from oxidation in vivo. Because the time course of increase in LDL oxidation in vivo during APR (in the present study) follows the time course of LPS-induced decrease in paraoxonase activity,20 the decreased paraoxonase activity during APR is likely to be a potential mechanism for the increased oxidation of circulating LDL reported herein.
In addition to paraoxonase, other HDL-associated proteins also could contribute to increased LDL oxidation during the APR. Plasma ceruloplasmin levels are increased during APR,39 and purified ceruloplasmin has been shown to increase oxidation of LDL in cell-free systems as well as in cultured endothelial, smooth muscle, and U937 monocytic cells.40 Because both LPS and zymosan increase ceruloplasmin levels,39 40 it is possible that an increase in ceruloplasmin during infection and inflammation could increase LDL oxidation.
Transferrin is another metal-binding protein associated with HDL.41 Hepatic synthesis and serum levels of transferrin are decreased during APR.42 Removal of HDL subpopulations that contain transferrin reduces the ability of HDL to protect against LDL oxidation in vitro.41 Thus, a decrease in transferrin synthesis during APR may lead to less transferrin in HDL, which makes it less effective for protection of LDL against oxidation.
We also found increased LPC levels in circulating LDL after LPS treatment. LPC is known to exert several proatherogenic effects and is a marker for oxidative modification of LDL.15 LPC is produced by hydrolysis of phosphatidylcholine, a reaction primarily mediated by plasma PAF-AH, an enzyme associated with lipoproteins.32 Plasma PAF-AH activity is increased in Syrian hamsters, rats, and mice after LPS, zymosan, or turpentine treatment.33 Plasma PAF-AH activity is also higher in patients with human immunodeficiency virus infection.43 Because the time course of LPS-induced increase in LPC content in circulating LDL in Syrian hamsters follows that of lipid oxidation (reported in the present study) and plasma PAF-AH activity,33 it is possible that the increase in LPC levels in LDL is secondary to an increase in plasma PAF-AH activity.
Several studies have shown that APR is accompanied by many proatherogenic changes in lipoprotein metabolism, such as a more-atherogenic lipoprotein profile that consists of increases in serum triglycerides and small, dense LDL and a decrease in HDL.10 11 12 13 APR is also accompanied by decreases in mRNA levels and activity of lecithin-cholesterol acyltransferase, cholesteryl ester transfer protein, and hepatic lipase (reviewed in reference 44 ). These decreases could decrease reverse-cholesterol transport. ApoA1 levels are also decreased during APR.45 Because apoA1 prevents the aggregation of LDL,46 decreased apoA1 during APR may facilitate LDL aggregation. Additionally, we have recently reported that lipoproteins isolated from Syrian hamsters treated with LPS are enriched in ceramides and sphingomyelin.47 An increase in LDL ceramide facilitates LDL aggregation and enhances its uptake by macrophages, which leads to foam cell formation.48 Finally, the present results demonstrate increased oxidized lipids in serum and circulating LDL during APR, which supports the hypothesis that the sustained host response to infection and inflammation may be proatherogenic, albeit through multiple mechanisms.
The present study raises a question as to why lipoprotein oxidation would occur during APR, a host reaction to infection and inflammation. The APR is thought to be a protective mechanism to prevent systemic injury and help the repair process. Lipoprotein oxidation during APR initially is likely to serve a beneficial purpose. Reactive oxygen species and free radicals are part of the local host defense mechanisms, given that they play a role in killing invading microorganisms and are induced by the same stimuli that induce APR.9 Thus, lipoproteins may scavenge these free radicals to prevent systemic toxicity and membrane damage. However, in doing so, lipoproteins may get oxidized. One of the major enzymes that plays a key role in microbial killing, myeloperoxidase, is acutely released by activated neutrophils and monocytes in response to LPS and other inflammatory stimuli.49 Myeloperoxidase also plays an important role in the oxidation of protein and lipid components of LDL and is expressed in atherosclerotic lesions.50 Moreover, LPS acutely induces the expression of lipoxygenases51 to increase the synthesis of prostaglandins and leukotrienes during the inflammatory response. Lipoxygenases also participate in LDL oxidation by oxidizing fatty acids, cholesteryl esters, and phospholipids.52 Because the activation of myeloperoxidase and lipoxygenases after LPS administration or other inflammatory stimuli occurs rapidly49 51 compared with LDL oxidation, which takes about 24 hours, it is unclear whether these enzymes participate in LDL oxidation during APR. Early activation of myeloperoxidase or lipoxygenase may initiate the oxidative process, which then accelerates after the depletion of paraoxonase or transferrin or after the upregulation of ceruloplasmin. Further studies are required to understand fully the metabolic changes that occur during APR and contribute to lipoprotein oxidation.
In summary, the present study demonstrates that the host response to infection and inflammation induces LDL oxidation in vivo. Moreover, the LDL that has been oxidized in vivo is more susceptible to further ex vivo oxidation and has a significantly shorter lag time. Increased LDL oxidation that occurs during infection and inflammation could be one of the mechanisms that promote atherosclerosis in patients with chronic infections and inflammatory diseases.
| Acknowledgments |
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Received December 14, 1999; accepted February 4, 2000.
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D. Zhang, Z. Bi, Y. Li, H. Zheng, L. Li, J. Ouyang, B. Wang, and Y. Bi Sodium Ferulate Modified Gene Expression Profile of Oxidized Low-Density Lipoprotein-Stimulated Human Umbilical Vein Endothelial Cells Journal of Cardiovascular Pharmacology and Therapeutics, December 1, 2009; 14(4): 302 - 313. [Abstract] [PDF] |
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C. Cuaz-Perolin, L. Billiet, E. Bauge, C. Copin, D. Scott-Algara, F. Genze, B. Buchele, T. Syrovets, T. Simmet, and M. Rouis Antiinflammatory and Antiatherogenic Effects of the NF-{kappa}B Inhibitor Acetyl-11-Keto-{beta}-Boswellic Acid in LPS-Challenged ApoE-/- Mice Arterioscler Thromb Vasc Biol, February 1, 2008; 28(2): 272 - 277. [Abstract] [Full Text] [PDF] |
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C. Kishimoto A Novel Approach to the Suppression of Atherosclerosis by Fc{gamma} Receptor Blockade Circ. Res., November 24, 2006; 99(11): 1154 - 1155. [Full Text] [PDF] |
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A. Kontush and M. J. Chapman Functionally Defective High-Density Lipoprotein: A New Therapeutic Target at the Crossroads of Dyslipidemia, Inflammation, and Atherosclerosis Pharmacol. Rev., September 1, 2006; 58(3): 342 - 374. [Abstract] [Full Text] [PDF] |
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P. Aspichueta, B. Perez-Agote, S. Perez, B. Ochoa, and O. Fresnedo Impaired response of VLDL lipid and apoB secretion to endotoxin in the fasted rat liver Innate Immunity, June 1, 2006; 12(3): 181 - 191. [Abstract] [PDF] |
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B. J. Ansell, K. E. Watson, A. M. Fogelman, M. Navab, and G. C. Fonarow High-Density Lipoprotein Function: Recent Advances J. Am. Coll. Cardiol., November 15, 2005; 46(10): 1792 - 1798. [Abstract] [Full Text] [PDF] |
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L. Tormakangas, L. Erkkila, T. Korhonen, T. Tiirola, A. Bloigu, P. Saikku, and M. Leinonen Effects of Repeated Chlamydia pneumoniae Inoculations on Aortic Lipid Accumulation and Inflammatory Response in C57BL/6J Mice Infect. Immun., October 1, 2005; 73(10): 6458 - 6466. [Abstract] [Full Text] [PDF] |
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P. J. Pussinen, T. Vilkuna-Rautiainen, G. Alfthan, T. Palosuo, M. Jauhiainen, J. Sundvall, M. Vesanen, K. Mattila, and S. Asikainen Severe Periodontitis Enhances Macrophage Activation via Increased Serum Lipopolysaccharide Arterioscler Thromb Vasc Biol, November 1, 2004; 24(11): 2174 - 2180. [Abstract] [Full Text] [PDF] |
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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] |
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D. Recalde, M. A. Ostos, E. Badell, A.-L. Garcia-Otin, J. Pidoux, G. Castro, M. M. Zakin, and D. Scott-Algara Human Apolipoprotein A-IV Reduces Secretion of Proinflammatory Cytokines and Atherosclerotic Effects of a Chronic Infection Mimicked by Lipopolysaccharide Arterioscler Thromb Vasc Biol, April 1, 2004; 24(4): 756 - 761. [Abstract] [Full Text] [PDF] |
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F. Coutant, S. Agaugue, L. Perrin-Cocon, P. Andre, and V. Lotteau Sensing Environmental Lipids by Dendritic Cell Modulates Its Function J. Immunol., January 1, 2004; 172(1): 54 - 60. [Abstract] [Full Text] [PDF] |
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P. Holvoet, T. B. Harris, R. P. Tracy, P. Verhamme, A. B. Newman, S. M. Rubin, E. M. Simonsick, L. H. Colbert, and S. B. Kritchevsky Association of High Coronary Heart Disease Risk Status With Circulating Oxidized LDL in the Well-Functioning Elderly: Findings From the Health, Aging, and Body Composition Study Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1444 - 1448. [Abstract] [Full Text] [PDF] |
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S. Kobayashi, N. Inoue, Y. Ohashi, M. Terashima, K. Matsui, T. Mori, H. Fujita, K. Awano, K. Kobayashi, H. Azumi, et al. Interaction of Oxidative Stress and Inflammatory Response in Coronary Plaque Instability: Important Role of C-Reactive Protein Arterioscler Thromb Vasc Biol, August 1, 2003; 23(8): 1398 - 1404. [Abstract] [Full Text] [PDF] |
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Z. Yuan, C. Kishimoto, H. Sano, K. Shioji, Y. Xu, and M. Yokode Immunoglobulin treatment suppresses atherosclerosis in apolipoprotein E-deficient mice via the Fc portion Am J Physiol Heart Circ Physiol, July 11, 2003; 285(2): H899 - H906. [Abstract] [Full Text] [PDF] |
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F. Locatelli, B. Canaud, K.-U. Eckardt, P. Stenvinkel, C. Wanner, and C. Zoccali Oxidative stress in end-stage renal disease: an emerging threat to patient outcome Nephrol. Dial. Transplant., July 1, 2003; 18(7): 1272 - 1280. [Abstract] [Full Text] [PDF] |
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B. Bayes, M. C. Pastor, J. Bonal, J. Junca, J. M. Hernandez, N. Riutort, A. Foraster, and R. Romero Homocysteine, C-reactive protein, lipid peroxidation and mortality in haemodialysis patients Nephrol. Dial. Transplant., January 1, 2003; 18(1): 106 - 112. [Abstract] [Full Text] [PDF] |
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F. Coutant, L. Perrin-Cocon, S. Agaugue, T. Delair, P. Andre, and V. Lotteau Mature Dendritic Cell Generation Promoted by Lysophosphatidylcholine J. Immunol., August 15, 2002; 169(4): 1688 - 1695. [Abstract] [Full Text] [PDF] |
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P. Stenvinkel Endothelial dysfunction and inflammation--is there a link? Nephrol. Dial. Transplant., October 1, 2001; 16(10): 1968 - 1971. [Full Text] [PDF] |
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M. Haidari, E. Javadi, M. Kadkhodaee, and A. Sanati Enhanced Susceptibility to Oxidation and Diminished Vitamin E Content of LDL from Patients with Stable Coronary Artery Disease Clin. Chem., July 1, 2001; 47(7): 1234 - 1240. [Abstract] [Full Text] [PDF] |
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W. Khovidhunkit, J. K. Shigenaga, A. H. Moser, K. R. Feingold, and C. Grunfeld Cholesterol efflux by acute-phase high density lipoprotein: role of lecithin:cholesterol acyltransferase J. Lipid Res., June 1, 2001; 42(6): 967 - 975. [Abstract] [Full Text] |
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B. J. Van Lenten, A. C. Wagner, D. P. Nayak, S. Hama, M. Navab, and A. M. Fogelman High-Density Lipoprotein Loses Its Anti-Inflammatory Properties During Acute Influenza A Infection Circulation, May 8, 2001; 103(18): 2283 - 2288. [Abstract] [Full Text] [PDF] |
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M. Navab, J. A. Berliner, G. Subbanagounder, S. Hama, A. J. Lusis, L. W. Castellani, S. Reddy, D. Shih, W. Shi, A. D. Watson, et al. HDL and the Inflammatory Response Induced by LDL-Derived Oxidized Phospholipids Arterioscler Thromb Vasc Biol, April 1, 2001; 21(4): 481 - 488. [Abstract] [Full Text] [PDF] |
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D. P. Hajjar Oxidized Lipoproteins and Infectious Agents : Are They in Collusion to Accelerate Atherogenesis? Arterioscler Thromb Vasc Biol, June 1, 2000; 20(6): 1421 - 1422. [Full Text] [PDF] |
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