Absence of Monocyte Chemoattractant Protein-1 Reduces Atherosclerosis in Low Density Lipoprotein Receptor–Deficient Mice

Gu, Lin; Okada, Yoshinori; Clinton, Steven K.; Gérard, Craig; Sukhova, Galina K.; Libby, Peter; Rollins, Barrett J.

doi:10.1016/s1097-2765(00)80139-2

Cited by 1,432 publications

(922 citation statements)

References 47 publications

Supporting

Mentioning

848

Contrasting

Unclassified

Order By: Relevance

“…A role for MCP-1 in the initiation of atherogenesis was demonstrated by knockout mice in which the MCP-1 gene itself or its receptor CCR2 was inactivated. 24,25 In our study, we demonstrated that serum MCP-1 concentrations are significantly lower in IL-10-transduced mice than in control mice. In addition, we observed enhanced MCP-1 expression in the vascular wall of ApoE-deficient mice, as reported previously, 26 which was significantly inhibited by IL-10 gene transfer.…”

Section: Discussionsupporting

confidence: 47%

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice

et al. 2004

View full text Add to dashboard Cite

Inflammation is a major contributor to atherosclerosis by its effects on arterial wall biology and lipoprotein metabolism. Interleukin-10 (IL-10) is an anti-inflammatory cytokine that may modulate the atherosclerotic disease process. We investigated the effects of adeno-associated virus (AAV) vector-mediated gene transfer of IL-10 on atherogenesis in apolipoprotein E (ApoE)-deficient mice. A murine myoblast cell line, C2C12, transduced with AAV encoding murine IL-10 (AAV2-mIL10) secreted substantial amounts of IL-10 into conditioned medium. The production of monocyte chemoattractant protein-1 (MCP-1) by the murine macrophage cell line, J774, was significantly inhibited by conditioned medium from AAV2-mIL10-transduced C2C12 cells. ApoE-deficient mice were injected with AAV5-mIL10 into their anterior tibial muscle at 8 weeks of age. The expression of MCP-1 in the vascular wall of the ascending aorta and serum MCP-1 concentration were decreased in AAV5-mIL10-transduced mice compared with AAV5-LacZ-transduced mice. Oil red-O staining of the ascending aorta revealed that IL-10 gene transfer resulted in a 31% reduction in plaque surface area. Serum cholesterol concentrations were also significantly reduced in AAV5-mIL10-transduced mice. To understand the cholesterol-lowering mechanism of IL-10, we measured the cellular cholesterol level in HepG2 cells, resulting in its significant decrease by the addition of IL-10 in a dosedependent manner. Furthermore, IL-10 suppressed HMGCoA reductase expression in the HepG2 cells. These observations suggest that intramuscular injection of AAV5-mIL10 into ApoE-deficient mice inhibits atherogenesis through anti-inflammatory and cholesterol-lowering effects.

show abstract

Section: Discussionsupporting

confidence: 47%

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice

et al. 2004

View full text Add to dashboard Cite

show abstract

“…43 Furthermore, knocking out MCP-1 or its receptor in LDL Ϫ/Ϫ or ApoE Ϫ/Ϫ mice, respectively, will also significantly decrease lesion formation. 44,45 In conclusion, adhesion and transmigration mediated by several interacting molecular mechanisms appear to be essential for monocyte traffic in atherosclerosis, and this study provides further evidence of the importance of these phenomena in the pathogenesis of the disease.…”

Section: Bourdillon Et Al Vascular Lesions In Apoe/icam-1-deficient Micesupporting

confidence: 52%

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE ⁻ ^/− /ICAM-1 ⁻ ^/− ) Fed a Fat or a Chow Diet

Bourdillon

Poston

Covacho

et al. 2000

ATVB

144

View full text Add to dashboard Cite

Abstract-Intercellular adhesion molecule (ICAM)-1, a major adhesion molecule, plays a critical role in the homing of leukocytes to sites of atherosclerotic lesions. However, very little is known on the role of ICAM-1 in initiating and perpetuating vascular lesions in ApoE Ϫ/Ϫ mice fed a chow or a fat diet. This study has investigated the mean aortic lesions in mice (C57BL6 background) with a single-knockout (ApoE Ϫ/Ϫ ) or double-knockout (DKO; ApoE Ϫ/Ϫ , ICAM-1 Ϫ/Ϫ ) fed a chow or a fat diet over a period of 3, 6, 15, and 20 weeks. A 3-fold reduction in lesion size was observed at all time points in DKO mice fed a chow diet. However, in DKO mice fed a fat diet, a marked reduction in the aortic lesion was observed at 3 and 15 weeks, which did not reach a significant level at 6 and 20 weeks. This study shows in essence that DKO mice are protected from developing significant lesions for up to 6 weeks when fed a chow diet and from 3 to 6 weeks when fed a fat diet. After 6 weeks, the lesion size of the DKO mice follows that of the single-knockout mice when fed a chow diet and gets to the same level in mice fed a fat diet. Plasma cholesterol levels were not altered as a result of ICAM-1 deficiency. These studies show that ICAM-1 is implicated in the formation and progression of atherosclerotic lesions.

show abstract

“…Atherosclerosisprone mice deficient in MCP-1 (MCP1 À/À ) or its receptor CCR2 (CCR2 À/À ) have smaller and decreased numbers of lesions compared to wild-type mice. 1,2 Evidence for a role for MCP-1 in atherogenesis has also been reported in human tissue. MCP-1 expression was upregulated in human atheromatous plaques compared to normal tissue 3 and in endothelial and smooth muscle cells exposed to modified low-density lipoprotein (LDL).…”

Section: Introductionmentioning

confidence: 93%

Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI Family Heart Study follow-up examination

et al. 2007

View full text Add to dashboard Cite

Atherogenesis is a chronic inflammatory process. Critical in the inflammation process is monocyte chemoattractant protein-1 (MCP-1). To locate genomic regions that affect circulating MCP-1 levels, a genome-wide linkage scan was conducted in a sample of whites and blacks. Phenotype and genetic marker data were available for 2501 white and 513 black participants in the National Heart Lung Blood Institute Family Heart Study follow-up examination. Heritability for MCP-1 was 0.37 in whites and 0.47 in blacks after adjusting for the effects of sex, age, age-sex interaction, smoking status, lifetime smoking exposure (pack-years) and field center. Significant linkage was observed for MCP-1 in a combined black and white sample on chromosome 3 (logarithm of the odds ratio (LOD) ¼ 3.5 at 78 cM, P ¼ 0.0001) and suggestive linkage was observed in whites on chromosome 5 (LOD ¼ 1.8 at 128 cM, P ¼ 0.002). Located under the linkage peak on chromosome 3 is the chemokine receptor gene cluster, including CCR2, the receptor for MCP-1. This study provides preliminary evidence linking genetic variation in a receptor to circulating levels of its ligand, as previously demonstrated for the low-density lipoprotein receptor. Further characterization of these chromosomal regions is needed to identify the functional mutations associated with circulating levels of MCP-1.

show abstract

Absence of Monocyte Chemoattractant Protein-1 Reduces Atherosclerosis in Low Density Lipoprotein Receptor–Deficient Mice

Cited by 1,432 publications

References 47 publications

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE ⁻ ^/− /ICAM-1 ⁻ ^/− ) Fed a Fat or a Chow Diet

Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI Family Heart Study follow-up examination

Contact Info

Product

Resources

About

Absence of Monocyte Chemoattractant Protein-1 Reduces Atherosclerosis in Low Density Lipoprotein Receptor–Deficient Mice

Cited by 1,432 publications

References 47 publications

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice

Adeno-associated virus vector-mediated interleukin-10 gene transfer inhibits atherosclerosis in apolipoprotein E-deficient mice

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE − /− /ICAM-1 − /− ) Fed a Fat or a Chow Diet

Circulating MCP-1 levels shows linkage to chemokine receptor gene cluster on chromosome 3: the NHLBI Family Heart Study follow-up examination

Contact Info

Product

Resources

About

ICAM-1 Deficiency Reduces Atherosclerotic Lesions in Double-Knockout Mice (ApoE ⁻ ^/− /ICAM-1 ⁻ ^/− ) Fed a Fat or a Chow Diet