© 2000 American Heart Association, Inc.
Integrative Physiology |
Determinants of Atherosclerosis Susceptibility in the C3H and C57BL/6 Mouse Model
Evidence for Involvement of Endothelial Cells but Not Blood Cells or Cholesterol Metabolism
From the Department of Medicine and Department of Microbiology and Molecular Genetics, University of California, Los Angeles.
Correspondence to Dr Aldons J. Lusis, Department of Medicine, UCLA, 47-123 CHS, Los Angeles, CA 90095-1679. E-mail jlusis{at}medicine.medsch.ucla.edu
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Abstract |
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Abstract—Lipids, monocytes, and arterial wall cells are primary components involved in atherogenesis. Using the inbred mouse strains C57BL/6J (B6) and C3H/HeJ (C3H), which have been extensively studied as models of the genetic control of diet-induced atherosclerosis, we examined which of these components determine genetic susceptibility. To test whether dietary responsiveness is involved, a congenic strain of C3H carrying an apoE-null allele (apoE-/-) was constructed. Although C3H.apoE-/- mice had higher plasma cholesterol levels, they developed much smaller lesions than their B6.apoE-/- counterpart on either chow or Western diets. Reciprocal bone marrow transplantation between the strains, with congenics carrying the same H-2 haplotype, was performed to examine the role of monocytes. The atherosclerosis susceptibility was not altered in the recipient mice, indicating that variations in monocyte function were not involved. Endothelial cells isolated from the aorta of B6 mice exhibited a dramatic induction of monocyte chemotactic protein-1, macrophage colony–stimulating factor, vascular cell adhesion molecule-1, and heme oxygenase-1 in response to minimally modified LDL, whereas endothelial cells from C3H mice showed little or no induction. In a set of recombinant inbred strains derived from the B6 and C3H parental strains, endothelial responses to minimally modified LDL cosegregated with aortic lesion size. These data provide strong evidence that endothelial cells, but not monocytes or plasma lipid levels, account for the difference in susceptibility to atherosclerosis between the 2 mouse strains.
Key Words: hyperlipidemia • monocytes • endothelium • cells • atherosclerosis • inbred strains
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Introduction |
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Atherosclerosis is a complex disease of the large and medium-sized arteries that results from interactions among lipids, monocytes, and arterial wall cells.1 2 Increases in plasma LDL levels or decreases in HDL levels are major risk factors for the development of atherosclerosis.3 4 Endothelial cells (ECs) have been considered to play a crucial role in initiation of the disease.2 They oxidatively modify LDL, and in response to oxidized LDL or its components, ECs express monocyte chemotactic protein-1 (MCP-1), macrophage colony–stimulating factor (M-CSF), vascular cell adhesion molecule-1 (VCAM-1), and other adhesion molecules and growth factors that promote monocyte transmigration into the subendothelium and differentiation into macrophages.5 6 7 8 Subsequently, the macrophages ingest modified LDL to give rise to foam cells, the hallmark of early atherosclerosis. Monocytes are the primary source of foam cells in atherosclerotic lesions.9 There is convincing evidence that circulating monocytes significantly influence atherosclerosis progression in mouse models. The absence of M-CSF, a growth factor for monocyte-macrophages, markedly reduced atherosclerotic lesions in fat-fed wild-type mice, apoE-/- mice, and LDL receptor–deficient mice.10 11 12 Also, the transplantation of bone marrow from apoE-/- mice into wild-type mice greatly increased lesion development.13
The variation in atherosclerosis susceptibility among inbred strains of mice provides a method of identifying the cellular and molecular interactions in atherogenesis.14 B6 and C3H mice are 2 commonly used inbred strains that differ strikingly in aortic fatty streak development when fed a high-fat, high-cholesterol diet with cholate. Because this atherogenic diet induces a marked reduction in plasma HDL levels of B6 mice but not in those of C3H mice, the alteration in HDL levels has been considered to be responsible for the difference in susceptibility.15 16 17 Genetic studies of the C3H and B6 mouse model have provided evidence for major gene effects,15 17 but the large nongenetic variance of lesion development has made genetic analysis difficult. The results of recent studies have suggested that inflammatory mechanisms may underlie the differences in susceptibility. We found that the atherogenic diet resulted in a dramatic induction in several inflammatory genes in the livers of B6 mice but not in those of C3H mice.18 Because of the small size of arteries in mice, these differences between the 2 strains have not been demonstrated at the level of arterial walls. The principal objective of the present study was to examine the contribution of lipids, monocytes, and ECs to atherosclerosis susceptibility and resistance in B6 and C3H mice.
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Materials and Methods |
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Construction of C3H.apoE-/- Mice
C3H.apoE-/- mice were created by crossing B6.apoE-/- mice with C3H/HeJ mice. The resulting heterozygous apoE+/- mice were then backcrossed to C3H mice for 4 generations. Mice homogeneous for the apoE-null allele on a C3H background were subsequently generated by brother-sister mating.
Bone Marrow Transplantation
Two-month-old male C57BL6/J and C3H.SW mice, which share the
same major histocompatible haplotype, H-2b, were
used for bone marrow transplantation (BMT). Recipient mice were
lethally irradiated. Bone marrow was harvested by flushing of the
femurs and tibias of donor mice. Each recipient mouse was injected with
107 bone marrow cells through the tail veins.
Two weeks after BMT, overnight-fasted mice were bled, and DNA from the blood was analyzed with the use of polymorphic markers. The mice that expressed donor DNA were fed for 12 weeks with the atherogenic diet.
Tissue Preparation and Lesion Analysis
The methods that were used for the quantification of
atheromatous lesions at the aortic root were as
previously reported.19
The en face measurement of aortic lesions was made in apoE-/- mice fed the Western diet. The aorta was stained with Sudan IV. The extent of the Sudan IV–positive area was quantified and expressed as a percent of the total aortic surface.
Plasma Lipid Measurements
Enzymatic assays for total and free cholesterol, HDL
cholesterol, and triglycerides were performed
as described by Hedrick et al.20
Lipoprotein Isolation and Modification
LDL was isolated from the serum of healthy human donors as
described by Havel et al.21 Minimally oxidized LDL was
prepared through incubation of LDL with 7 µmol/L
FeSO4 or 4 µmol/L
CuSO4 as described previously.22
Culture and Treatment of ECs
ECs from the thoracic aorta were isolated with an explantation
technique. The thoracic aorta was gently cleansed of periadventitial
fat and connective tissue and cut into rings 
3 mm in length.
The aortic segments were placed on Matrigel (Collaborative Research)
and incubated in DMEM supplemented with FBS, penicillin-streptomycin,
heparin, EC growth supplements, and fungizone. The vessel rings were
removed once cell outgrowth was observed. The cells were passaged with
Dispase (Collaborative Research) and plated onto gelatin-coated dishes.
The subsequent passages were performed with trypsin-EDTA. At passages
used for experiments, all cells expressed the von Willebrand
factor antigen and took up DiI-Ac-LDL.
Confluent cells at passages 4 to 6 were treated for 4 hours with 200 µg/mL native LDL, 200 µg/mL minimally modified (MM)-LDL, 2 µg/mL LPS, or medium only.
RNA Extraction and Northern Blot Analysis
Total RNA of the ECs was isolated with TRIzol Reagents (GIBCO)
according to the protocol from the manufacturer, fractionated on
agarose-formaldehyde gel, and transferred onto nylon membranes. The
blots were hybridized with 32P-labeled mouse cDNA
probes. The blots were exposed to Hyperfilm-ECL. The density of the
bands was quantified with a densitometer and standardized with
GAPDH.
Statistical Analysis
Data were presented as mean±SEM. ANOVA was used to
determine differences between groups in lesions or lipid levels. When
only 2 mean values were compared, the Student’s t test was
used. Differences were considered statistically significant at
P<0.05.
An expanded Materials and Methods section is available online at http://www.circresaha.org.
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Results |
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Plasma Lipid Levels and Aortic Lesions of C3H.apoE-Deficient Mice
Both B6.apoE-/- mice and C3H.apoE-/- mice exhibited hypercholesterolemia when on a normal chow diet, and it was aggravated by feeding the Western diet (Figure 1
). The total cholesterol,
free cholesterol, and triglyceride levels were
slightly higher in C3H.apoE-/- mice than in
B6.apoE-/- mice on either chow
(P=0.04) or Western diet (P<0.0001). On the
chow, there were no significant differences in HDL
cholesterol levels between
C3H.apoE-/- (20.2±7.3 mg/L) and
B6.apoE-/- mice (21.0±2.8 mg/L). On the
Western diet, HDL cholesterol levels were significantly
elevated in C3H.apoE-/- mice (118.8±11.1 mg/L)
(P=0.008) but not in B6.apoE-/- mice
(22.6±6.0 mg/L).
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At 12 weeks of age on the chow diet, the average area of aortic
atherosclerotic lesions per section per animal in
B6.apoE-/- mice was 19 321±2992
µm2 (n=15), but in
C3H.apoE-/- mice, only 3 of 11 mice had
lesions, with an average of 140±73 µm2
(Figure 2) (P<0.0001). After
16 weeks on the Western diet, which started at 8 weeks of age, the mean
area of aortic lesions was almost 10-fold greater in
B6.apoE-/- mice (n=15) than in
C3H.apoE-/- mice (n=10) (601 772±40 214
versus 63 000±5775 µm2)
(P<0.0001). The en face measurement of aortic lesions was
made in mice maintained on the Western diet. Significantly reduced
lesion development was detected in C3H.apoE-/-
mice (5.3±0.9% versus 10.4±0.74% in
B6.apoE-/- mice; P=0.0003).
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Effect of BMT on Atherosclerosis
To examine the role of monocytes in atherogenesis, BMT was
performed in 4 groups of mice: B6
C3H, C3HB6, B6B6, and
C3HC3H. In each group, 8 to 10 mice were used as recipients. An
analysis of serum cholesterol and
triglyceride levels 12 weeks after the atherogenic diet
showed no significant differences between the mice receiving bone
marrow from the other strain and those receiving bone marrow from the
same strain (Figure 3). The mean area of
aortic lesions was similar between groups C3HB6 and B6B6
(1477±496 versus 1503±472 µm2)
(P=0.97; Figure 4). In
addition, the mean lesion area between groups B6C3H and C3HC3H
did not differ (43±33 versus 130±113
µm2) (P=0.48).
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Responses of ECs to MM-LDL
As shown in Figure 5 and the
Table, MM-LDL, prepared with
Fe2+ or Cu2+ oxidation,
induced marked production of MCP-1, M-CSF, VCAM-1, and heme
oxygenase-1 (HO-1) mRNAs in ECs from susceptible B6 mice.
In contrast, ECs from resistant C3H mice showed small or no
induction of these mRNAs. Native LDL had no effect on gene induction in
ECs from either strain. Interestingly, LPS induced prominent but
similar expression of MCP-1, M-CSF, and VCAM-1 genes in both strains.
Unlike MM-LDL, LPS had little effect on HO-1 expression. As a
housekeeping gene, GAPDH mRNA was not induced. These results have been
confirmed with multiple independent cultures of ECs from the 2 strains
and with numerous separate preparations of oxidized LDL.
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The AOP2 gene maps to a region of chromosome 1 that has been thought to harbor a gene that contributes to atherogenesis in a genetic cross between B6 and C3H mice.15 23 ECs of both B6 and C3H mice expressed similar baseline levels of AOP2 mRNA, and neither MM-LDL nor LPS influenced expression of the gene.
In a set of recombinant inbred (RI) strains (designated BXH) derived
from the wild-type B6 and C3H strains, we examined the genetic
segregation between endothelial responses to MM-LDL and
atherosclerosis susceptibility. Because HO-1 mRNA was
induced by MM-LDL but not by LPS, its induction was used to
represent endothelial responses to MM-LDL. The
size of aortic lesions after the atherogenic diet was fed for 15 weeks
was used as the parameter for susceptibility to
atherosclerosis. MM-LDL resulted in HO-1 mRNA induction
in a strain-specific pattern, and strains with higher HO-1 induction
had larger lesions (Fe-LDL r=0. 57, P=0.0001;
Cu-LDL r=0.79, P=0.0013) (Figure 6). Native LDL and LPS had little effect
on HO-1 expression of ECs in these strains. These data indicate that EC
responses to oxidized LDL cosegregate with
atherosclerosis susceptibility.
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Discussion |
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Inbred mouse strains B6 and C3H have been studied extensively as a model of the genetic control of atherogenesis. In response to an atherogenic diet, B6 mice develop fatty streak lesions in the proximal aorta, whereas C3H mice are totally resistant to fatty streak formation. The present study was undertaken to determine the levels (plasma lipids, monocytes, and arterial wall cells) at which genetic variations affect atherogenesis in these 2 mouse strains.
In wild-type mouse models, atherosclerosis is induced
by feeding a high-fat, high-cholesterol diet that contains
cholate. In response to this diet, strain B6 mice have reduced levels
of HDL compared with C3H mice.15 Moreover, this diet
results in a reduction in serum paraoxonase, an HDL-associated enzyme
that protects against LDL oxidation, in B6 mice but not in C3H
mice.16 The apoE-/- mice
represent a mouse model in which spontaneous
hyperlipidemia and atherosclerosis
occur with a low-fat, low-cholesterol
diet.24 25 In the present study, we constructed
congenic apoE-/- mice on a C3H genetic
background by repeatedly backcrossing
B6.apoE-/- mice to C3H mice, with selection for
the apoE-null allele, followed by intercrossing to produce
homozygous apoE-null mice on the C3H background. The resulting
apoE-/- mice had a background of 96% C3H.
Consistent with the finding with the wild-type mice fed the
atherogenic diet, C3H.apoE-/- mice were highly
resistant to atherosclerosis, developing much
smaller lesions than B6.apoE-/- mice on either
chow or a Western diet. The resistance to
atherosclerosis is unlikely to be associated with HDL
levels because there were no significant differences in HDL levels
between the 2 strains of mice on the chow diet. As seen in wild-type
mice, the Western diet elevated the HDL level in
C3H.apoE-/- mice but not in
B6.apoE-/- mice. A recent study in which the
apoE-null allele was transferred onto the genetic background of
strain FVB/NT also revealed a strong effect of genetic background on
atherosclerosis susceptibility and plasma lipid
levels.26
Macrophage-derived foam cells are the principal cellular elements in early atherosclerotic lesions.9 Moreover, foam cells produce cytokines and growth factors that play an important role in the development and progression of atherosclerosis.27 In the present study, the role of monocytes/macrophages in atherosclerosis susceptibility was examined through reciprocal transplantation of the bone marrow of B6 and C3H mice. B6 and C3H mice differ in their MHC haplotype. To avoid graft rejection, we used C3H.SW mice, which have the same MHC haplotype, H-2b, as B6 mice, for transplantation. C3H.SW and C3H/HeJ mice are genetically identical except for the MHC locus. We observed that neither the extent of aortic atherosclerotic lesions nor the plasma lipid levels were significantly affected by BMT. These results indicate that monocytes (or other blood elements) do not play an important role in the genetic difference in atherosclerosis susceptibility between the 2 strains.
We used 2 different models (dietary and apoE knockout) to
determine the influence of monocytes and plasma lipids on
atherosclerosis susceptibility of B6 and C3H mice. This
raises the concern that the genetic control of
atherosclerosis susceptibility may differ between the 2
models. However, the 2 models have yielded generally consistent
findings in a number of studies. For example, the expression of a human
apoA-I transgene dramatically reduced lesion formation in both
models.28 Similarly, a null mutation of M-CSF nearly
abolished lesion formation in both models.10 11 In
addition, T or B lymphocyte deficiencies exhibited similar effects in
the 2 models.29 30 Finally, recent studies have shown that
a null mutation of paraoxonase increased lesion formation 2-fold in
both models (D.M.S. and A.J.L., unpublished
observations).31
Accumulated evidence indicates that LDL oxidation plays an important
role in atherogenesis.1 2 32 Minimally or mildly oxidized
species of LDL are potent inducers of inflammatory genes. Among them,
M-CSF, MCP-1, and VCAM-1 are highly elevated in atherosclerotic lesions
compared with normal artery and highly induced in ECs by oxidized
LDL.5 6 8 33 34 35 HO-1, an enzyme that catabolizes heme to
biliverdin, carbon monoxide, and free iron, is a sensitive indicator of
cellular oxidative stress and is highly elevated in atherosclerotic
lesions.36 37 38 The present data clearly show that ECs
from susceptible B6 mice exhibit induction of mRNA for MCP-1, M-CSF,
VCAM-1, and HO-1 in response to MM-LDL, whereas ECs from C3H mice
exhibit little or no induction (Figure 5
). In contrast to
MM-LDL, LPS induced similar expression of MCP-1, M-CSF, and VCAM-1 in
ECs from the 2 strains and had no effect on HO-1 expression. These
findings are consistent with the observation that in ECs,
MM-LDL specifically induces adhesion molecules for monocytes, whereas
LPS induces adhesion molecules for both neutrophils and
monocytes.39 Our results are in agreement with previous in
vivo findings that the injection of MM-LDL or the feeding of an
atherogenic diet induced a greater production of MCP-1, M-CSF,
and HO-1 in B6 mice than in C3H mice.18 40
To determine whether endothelial responsiveness to
MM-LDL is associated with genetic susceptibility to
atherosclerosis, we examined
endothelial responses to MM-LDL in a set of RI strains
derived from the wild-type B6 and C3H mice. Each RI strain
represents a unique mixture of genes derived from the parental
strains, and depending on the combination of genes that was inherited,
each strain exhibits a particular degree of susceptibility to
atherosclerosis. In the present study, we examined
the induction of HO-1 mRNA because it was highly induced by MM-LDL but
was not by LPS. We found that endothelial responses to
MM-LDL segregated with the susceptibility to aortic atherosclerotic
lesions (Figure 6). This finding provides genetic evidence that
variations in endothelial responses to MM-LDL are
closely linked with aortic atherosclerotic lesion formation. Thus, it
is likely that feeding of the atherogenic diet to mice results in lipid
accumulation in the aorta and other arteries, where the lipids become
oxidatively modified. The oxidized lipids then stimulate ECs to express
MCP-1, M-CSF, VCAM-1, and other proinflammatory molecules, resulting in
monocyte infiltration and foam cell formation. It appears that because
the ECs of B6 mice are much more responsive to oxidized lipoproteins
than are the ECs of C3H mice, the degree of inflammation and monocyte
infiltration is greater in B6 than in C3H mice.
The AOP2 gene, which encodes an antioxidant protein, maps to distal
mouse chromosome 1 near the putative location of the Ath-1
gene.23 A recent study suggested that the AOP2 gene
may in fact correspond to Ath-1.41
Our present results do not support this conclusion, because no
differences were observed in AOP2 expression between strains in
response to MM-LDL (Figure 5).
In C3H mice, a naturally occurring mutation on chromosome 4 renders most cells, including lymphocytes and macrophages, insensitive to LPS-induced cytokine release.42 A recent study showed that the LPS allele of C3H mice corresponds to a missense mutation in exon 3 of the Toll-like receptor-4 gene.43 The Toll-like receptor-4 has been suggested to transduce the LPS signal across the plasma membrane. However, our present results indicated that ECs from C3H mice were as responsive to LPS as those from B6 mice with respect to MCP-1, M-CSF, and VCAM-1 mRNA induction. These data suggest that receptor subtypes on ECs that mediate the effect of LPS may differ from those on lymphocytes and macrophages.
The demonstration that the differences in atherosclerosis susceptibility between inbred mouse strains B6 and C3H are due, at least in part, to genetic differences in endothelial responses provides the first clear evidence for genetic factors in atherosclerosis that act at the level of the vessel wall.
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Acknowledgments |
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This work was supported by National Institutes of Health grant HL-30568.
Received January 7, 2000; accepted March 29, 2000.
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References |
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TopAbstractIntroductionMaterials and MethodsResultsDiscussionReferences |
|---|
1. Steinberg D. Low density lipoprotein oxidation and its pathobiological significance. J Biol Chem. 1997;272:20963–20966.
2.
Berliner JA, Navab M, Fogelman AM, Frank JS, Demer LL,
Edwards PA, Watson AD, Lusis AJ. Atherosclerosis: basic
mechanisms: oxidation, inflammation, and genetics.
Circulation. 1995;91:2488–2496.
3.
The Lipid Research Clinics Coronary Primary
Prevention Trial results. I. Reduction in incidence of coronary
heart disease. JAMA. 1984;251:351–364.
4.
Gordon DJ, Probstfield JL, Garrison RJ, Neaton JD,
Castelli WP, Knoke JD, Jacobs DR Jr, Bangdiwala S, Tyroler HA.
High-density lipoprotein cholesterol and
cardiovascular disease: four prospective American
studies. Circulation. 1989;79:8–15.
5.
Cushing SD, Berliner JA, Valente AJ, Territo MC, Navab
M, Parhami F, Gerrity R, Schwartz CJ, Fogelman AM. Minimally modified
low density lipoprotein induces monocyte chemotactic protein 1 in human
endothelial cells and smooth muscle cells. Proc
Natl Acad Sci U S A. 1990;87:5134–5138.
6. Rajavashisth TB, Andalibi A, Territo MC, Berliner JA, Navab M, Fogelman AM, Lusis AJ. Induction of endothelial cell expression of granulocyte and macrophage colony-stimulating factors by modified low-density lipoproteins. Nature. 1990;344:254–257.[Medline] [Order article via Infotrieve]
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. Khan BV, Parthasarathy SS, Alexander RW, Medford RM. Modified low density lipoprotein and its constituents augment cytokine-activated vascular cell adhesion molecule-1 gene expression in human vascular endothelial cells. J Clin Invest. 1995;95:1262–1270.
9. Gerrity RG. The role of the monocyte in atherogenesis, I: transition of blood-borne monocytes into foam cells in fatty lesions. Am J Pathol. 1981;103:181–190.[Abstract]
10.
Smith JD, Trogan E, Ginsberg M, Grigaux C, Tian J,
Miyata M. Decreased atherosclerosis in mice deficient
in both macrophage colony-stimulating factor (op) and
apolipoprotein E. Proc Natl Acad Sci U S A. 1995;92:8264–8268.
11. Qiao JH, Tripathi J, Mishra NK, Cai Y, Tripathi S, Wang XP, Imes S, Fishbein MC, Clinton SK, Libby P, Lusis AJ, Rajavashisth TB. Role of macrophage colony-stimulating factor in atherosclerosis: studies of osteopetrotic mice. Am J Pathol. 1997;150:1687–1699.[Abstract]
12. Rajavashisth T, Qiao JH, Tripathi S, Tripathi J, Mishra N, Hua M, Wang XP, Loussararian A, Clinton S, Libby P, Lusis AJ. Heterozygous osteopetrotic (op) mutation reduces atherosclerosis in LDL receptor-deficient mice. J Clin Invest. 1998;101:2702–2710.[Medline] [Order article via Infotrieve]
13.
Fazio S, Babaev VR, Murray AB, Hasty AH, Carter KJ,
Gleaves LA, Atkinson JA, Linton MF. Increased
atherosclerosis in mice reconstituted with
apolipoprotein E null macrophages. Proc Natl Acad Sci
U S A. 1997;94:4647–4652.
14. Paigen B, Morrow A, Brandon C, Mitchell D, Holmes P. Quantitative assessment of atherosclerotic lesions in mice. Atherosclerosis. 1985;57:65–73.[Medline] [Order article via Infotrieve]
15.
Paigen B, Mitchell D, Reue K, Morrow A, Lusis AJ,
LeBoeuf RC. Ath-1, a gene determining atherosclerosis
susceptibility and high density lipoprotein levels in mice. Proc
Natl Acad Sci U S A. 1987;84:3763–3767.
16. Shih DM, Gu L, Hama S, Xia YR, 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]
17. Machleder D, Ivandic B, Welch C, Castellani L, Reue K, Lusis AJ. Complex genetic control of HDL levels in mice in response to an atherogenic diet: coordinate regulation of HDL levels and bile acid metabolism. J Clin Invest. 1997;99:1406–1419.[Medline] [Order article via Infotrieve]
18. Liao F, Andalibi A, deBeer FC, Fogelman AM, Lusis AJ. Genetic control of inflammatory gene induction and NF-kappa B-like transcription factor activation in response to an atherogenic diet in mice. J Clin Invest. 1993;91:2572–2579.
19.
Qiao JH, Xie PZ, Fishbein MC, Kreuzer J, Drake TA,
Demer LL, Lusis AJ. Pathology of atheromatous
lesions in inbred and genetically engineered mice: genetic
determination of arterial calcification. Arterioscler
Thromb. 1994;14:1480–1497.
20.
Hedrick CC, Castellani LW, Warden CH, Puppione DL,
Lusis AJ. Influence of mouse apolipoprotein A-II on plasma
lipoproteins in transgenic mice. J Biol Chem. 1993;268:20676–20682.
21. Havel RJ, Eder EA, Bragdon JH. The distribution and chemical composition of ultracentrifugally separated lipoproteins of human serum. J Clin Invest. 1955;43:1345–1353.
22.
Watson AD, Leitinger N, Navab M, Faull KF,
Hörkkö S, Witztum JL, Palinski W, Schwenke D, Salomon RG,
Sha W, Subbanagounder G, Fogelman AM, Berliner JA. Structural
identification by mass spectrometry of oxidized phospholipids in
minimally oxidized low density lipoprotein that induce
monocyte/endothelial interactions and evidence for
their presence in vivo. J Biol Chem. 1997;272:13597–13607.
23. Iakoubova OA, Pacella LA, Her H, Beier DR. LTW4 protein on mouse chromosome 1 is a member of a family of antioxidant proteins. Genomics. 1997;42:474–478.[Medline] [Order article via Infotrieve]
24. Plump AS, Smith JD, Hayek T, Aalto-Setälä K, Walsh A, Verstuyft JG, Rubin EM, Breslow JL. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell. 1992;71:343–353.[Medline] [Order article via Infotrieve]
25.
Zhang SH, Reddick RL, Piedrahita JA, Maeda N.
Spontaneous hypercholesterolemia and
arterial lesions in mice lacking apolipoprotein E.
Science. 1992;258:468–471.
26.
Dansky HM, Charlton SA, Sikes JL, Heath SC, Simantov R,
Levin LF, Shu P, Moore KJ, Breslow JL, Smith JD. Genetic background
determines the extent of atherosclerosis in
apoE-deficient mice. Arterioscler Thromb Vasc Biol. 1999;19:1960–1968.
27. Ross R. The pathogenesis of atherosclerosis: a perspective for the 1990s. Nature. 1993;362:801–809.[Medline] [Order article via Infotrieve]
28.
Plump AS, Scott CJ, Breslow JL. Human apolipoprotein
A-I gene expression increases high density lipoprotein and suppresses
atherosclerosis in the apolipoprotein E-deficient
mouse. Proc Natl Acad Sci U S A. 1994;91:9607–9611.
29. Fyfe AI, Qiao JH, Lusis AJ. Immune-deficient mice develop typical atherosclerotic fatty streaks when fed an atherogenic diet. J Clin Invest. 1994;94:2516–2520.
30.
Dansky HM, Charlton SA, Harper MM, Smith JD. T and B
lymphocytes play a minor role in atherosclerotic plaque formation in
the apolipoprotein E-deficient mouse. Proc Natl Acad Sci
U S A. 1997;94:4642–4646.
31. Shih DM, Gu L, Xia YR, Navab M, Li WF, Hama S, Castellani LW, Furlong CE, Costa LG, Fogelman AM, Lusis AJ. Mice lacking serum paraoxonase are susceptible to organophosphate toxicity and atherosclerosis. Nature. 1998;394:284–287.[Medline] [Order article via Infotrieve]
32. Steinberg D, Parthasarathy S, Carew TE, Khoo JC, Witztum JL. Beyond cholesterol: modifications of low-density lipoprotein that increase its atherogenicity. N Engl J Med. 1989;320:915–924.[Medline] [Order article via Infotrieve]
33.
Ylä-Herttuala S, Lipton BA, Rosenfeld ME,
Goldberg IJ, Steinberg D, Witztum JL. Macrophages and smooth
muscle cells express lipoprotein lipase in human and rabbit
atherosclerotic lesions. Proc Natl Acad Sci U S A. 1991;88:5252–5256.
34. Clinton SK, Underwood R, Hayes L, Sherman ML, Kufe DW, Libby P. Macrophage colony-stimulating factor gene expression in vascular cells and in experimental and human atherosclerosis. Am J Pathol. 1992;140:301–316.[Abstract]
35.
Nakashima Y, Raines EW, Plump AS, Breslow JL, Ross R.
Upregulation of VCAM-1 and ICAM-1 at
atherosclerosis-prone sites on the
endothelium in the apoE-deficient mouse.
Arterioscler Thromb Vasc Biol. 1998;18:842–851.
36.
Keyse SM, Tyrrell RM. Heme oxygenase is the
major 32-kDa stress protein induced in human skin fibroblasts by UVA
radiation, hydrogen peroxide, and sodium arsenite. Proc Natl Acad
Sci U S A. 1989;86:99–103.
37. Maines MD. The heme oxygenase system: a regulator of second messenger gases. Annu Rev Pharmacol Toxicol. 1997;37:517–554.[Medline] [Order article via Infotrieve]
38.
Stocker R, Yamamoto Y, McDonagh AF, Glazer AN, Ames BN.
Bilirubin is an antioxidant of possible
physiological importance. Science. 1987;235:1043–1046.
39. Berliner JA, Territo MC, Sevanian A, Ramin S, Kim JA, Bamshad B, Esterson M, Fogelman AM. Minimally modified low density lipoprotein stimulates monocyte endothelial interactions. J Clin Invest. 1990;85:1260–1266.
40. Liao F, Andalibi A, Qiao JH, 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.
41. Phelan SA, Johnson KA, Beier DR, Paigen B. Characterization of the murine gene encoding Aop2 (antioxidant protein 2) and identification of 2 highly related genes. Genomics. 1998;54:132–139.[Medline] [Order article via Infotrieve]
42. Vogel SN. The LPS gene: insights into the genetic and molecular basis of LPS responsiveness and macrophage differentiation. In: Beutler B, ed. Tumor Necrosis Factors: The Molecules and Their Emerging Role in Medicine. New York, NY: Raven Press Ltd; 1992: 485–513.
43.
Poltorak A, He X, Smirnova I, Liu MY, Huffel CV, Du X,
Birdwell D, Alejos E, Silva M, Galanos C, Freudenberg M,
Ricciardi-Castagnoli P, Layton B, Beutler B. Defective LPS signaling in
C3H/HeJ and C57BL/10ScCr mice: mutations in Tlr4 gene.
Science. 1998;282:2085–2088.
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|
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|
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|
|
|
|
|
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|
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|
|
|
|
|
|
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|
|
|
|
 |
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
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|
|
|
|
|
|
D. J. Rader and E. Pure Genetic Susceptibility to Atherosclerosis : Insights From Mice Circ. Res., May 26, 2000; 86(10): 1013 - 1015. [Full Text] [PDF]
|
|
|
|
|
|
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|
|
|
|
|
|
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