Atherosclerosis

2001

DOI: 10.1016/s0021-9150(00)00515-3

|View full text |Cite

|

Sign up to set email alerts

|

Atherosclerotic plaque rupture in the apolipoprotein E knockout mouse

Jason L. Johnson

¹

,

Christopher L. Jackson

²

Help me understand this report

Search citation statements

Order By: Relevance

Paper Sections

Select...

Discussion3

Introduction1

Mapping Genes For Atherosclerosis In Mice1

Citation Types

Supporting

5

Mentioning

147

Contrasting

1

Unclassified

2

Year Published

2001

2001

2007

2007

Publication Types

Select...

Article7

Book2

Other1

Relationship

Self Cite0

Independent10

Authors

Journals

Cited by 202 publications

(155 citation statements)

References 7 publications

Supporting

5

Mentioning

147

Contrasting

1

Unclassified

2

Order By: Relevance

“…Thus, because normal diet-fed apoE Ϫ/Ϫ mice do not develop unstable coronary plaques or suffer from spontaneous atherothrombotic events, despite their severe atherosclerosis, the convincing negative result of the present study is not surprising. More complex plaques have been reported in the innominate artery of aged fat-fed apoE Ϫ/Ϫ mice, with evidence of intra-plaque hemorrhage and atherothrombosis (57,58). These lesions merit further investigation in the human CRP transgenic model, especially in view of the report that arterial thrombosis is increased after vascular injury in human CRP transgenic mice (59).…”

Section: Discussionmentioning

confidence: 92%

Transgenic human C-reactive protein is not proatherogenic in apolipoprotein E-deficient mice

¹

,

²

,

³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The association between circulating concentrations of C-reactive protein (CRP) and future atherothrombotic events has provoked speculation about a possible pathogenetic role of CRP. However, we show here that transgenic expression of human CRP had no effect on development, progression, or severity of spontaneous atherosclerosis, or on morbidity or mortality, in male apolipoprotein E (apoE)-deficient C57BL͞6 mice up to 56 weeks, despite deposition of human CRP and mouse complement component 3 in the plaques. Although female apoE knockouts develop atherosclerosis more rapidly than males, the human CRP transgene is under sex hormone control and is expressed at human levels only in males. We therefore studied only male mice. The concentration of mouse serum amyloid P component, an extremely sensitive systemic marker of inflammation, remained normal throughout except for transient spikes in response to fighting in a few animals, indicating that atherogenesis in this model is not associated with an acute-phase response. However, among human CRP transgenic mice, the circulating CRP concentration was higher in apoE knockouts than in wild-type controls. The higher CRP values were associated with substantially lower estradiol concentrations in the apoE-deficient animals. Human CRP transgene expression is thus up-regulated in apoE-deficient mice, apparently reflecting altered estrogen levels, despite the absence of other systemic signs of inflammation. Extrapolation to human pathology from this xenogeneic combination of human CRP with apoE deficiency-mediated mouse atherosclerosis must be guarded. Nevertheless, the present results do not suggest that human CRP is either proatherogenic or atheroprotective in vivo.atherosclerosis ͉ inflammation ͉ transgenic

“…Thus, because normal diet-fed apoE Ϫ/Ϫ mice do not develop unstable coronary plaques or suffer from spontaneous atherothrombotic events, despite their severe atherosclerosis, the convincing negative result of the present study is not surprising. More complex plaques have been reported in the innominate artery of aged fat-fed apoE Ϫ/Ϫ mice, with evidence of intra-plaque hemorrhage and atherothrombosis (57,58). These lesions merit further investigation in the human CRP transgenic model, especially in view of the report that arterial thrombosis is increased after vascular injury in human CRP transgenic mice (59).…”

Section: Discussionmentioning

confidence: 92%

Transgenic human C-reactive protein is not proatherogenic in apolipoprotein E-deficient mice

¹

,

²

,

³

et al. 2005

Proc. Natl. Acad. Sci. U.S.A.

View full text Add to dashboard Cite

The association between circulating concentrations of C-reactive protein (CRP) and future atherothrombotic events has provoked speculation about a possible pathogenetic role of CRP. However, we show here that transgenic expression of human CRP had no effect on development, progression, or severity of spontaneous atherosclerosis, or on morbidity or mortality, in male apolipoprotein E (apoE)-deficient C57BL͞6 mice up to 56 weeks, despite deposition of human CRP and mouse complement component 3 in the plaques. Although female apoE knockouts develop atherosclerosis more rapidly than males, the human CRP transgene is under sex hormone control and is expressed at human levels only in males. We therefore studied only male mice. The concentration of mouse serum amyloid P component, an extremely sensitive systemic marker of inflammation, remained normal throughout except for transient spikes in response to fighting in a few animals, indicating that atherogenesis in this model is not associated with an acute-phase response. However, among human CRP transgenic mice, the circulating CRP concentration was higher in apoE knockouts than in wild-type controls. The higher CRP values were associated with substantially lower estradiol concentrations in the apoE-deficient animals. Human CRP transgene expression is thus up-regulated in apoE-deficient mice, apparently reflecting altered estrogen levels, despite the absence of other systemic signs of inflammation. Extrapolation to human pathology from this xenogeneic combination of human CRP with apoE deficiency-mediated mouse atherosclerosis must be guarded. Nevertheless, the present results do not suggest that human CRP is either proatherogenic or atheroprotective in vivo.atherosclerosis ͉ inflammation ͉ transgenic

“…Spontaneous plaque rupture has previously been observed in atherosclerosis-prone mouse strains. 31,32 In our model, however, rupture occurs more frequently and in a controlled fashion, allowing the delineation of the molecular pathways involved and the evaluation of therapies aimed at plaque stabilization and the prevention of acute cardiovascular events. Incidence of histological evidence of spontaneous and phenylephrine-induced plaque rupture in Ad5-CMV.lacZ-and Ad5-CMV.p53-treated, collarinduced lesions 14 days after adenovirus instillation.…”

Section: Discussionmentioning

confidence: 99%

Induction of Atherosclerotic Plaque Rupture in Apolipoprotein E ^−/− Mice After Adenovirus-Mediated Transfer of p53

¹

,

et al. 2002

View full text Add to dashboard Cite

Background-The presence of the tumor-suppressor gene p53 in advanced atherosclerotic plaques and the sensitivity to p53-induced cell death of smooth muscle cells isolated from these plaques have fueled speculation about the role of p53 in lesion destabilization and plaque rupture. In this study, we describe a strategy to promote (thrombotic) rupture of preexisting atherosclerotic lesions using p53-induced lesion remodeling. Methods and Results-Carotid atherogenesis was initiated in apolipoprotein E knockout mice by placement of a perivascular silastic collar. The resulting plaques were incubated transluminally with recombinant adenovirus carrying either a p53 or ␤-galactosidase (lacZ) transgene. p53 transfection was restricted to the smooth muscle cell-rich cap of the plaque and led to an increase in cap cell apoptosis 1 day after transfer. p53 overexpression resulted in a marked decrease in the cellular and extracellular content of the cap, reflected by a markedly reduced cap/intima ratio (0.21Ϯ0.04 versus 0.46Ϯ0.03, PϽ0.001). The latter is a characteristic feature of plaque vulnerability to rupture, and whereas spontaneous rupture of p53-treated lesions was rare, it was found in 40% of cases after treatment with the vasopressor compound phenylephrine (Pϭ0.003). Conclusions-We have demonstrated a potential role of p53-induced remodeling in atherosclerotic plaque destabilization.Being the first example of inducible rupture at a predefined location, this model offers a unique opportunity to delineate the processes that precede rupture and to evaluate plaque-stabilizing therapies.

“…Recently, some investigators have also observed spontaneous plaque rupture in the brachiocephalic arteries and subsequent sudden death in aged ApoE-/-mice [26][27][28][29]. These data suggest that ApoE-/-mice could be a useful model for the evaluation of tracers for detecting unstable atherosclerotic lesions.…”

Section: Introductionmentioning

confidence: 87%

Comparison of 99mTc-annexin A5 with 18F-FDG for the detection of atherosclerosis in ApoE−/− mice

¹

,

²

,

³

et al. 2007

Eur J Nucl Med Mol Imaging

View full text Add to dashboard Cite

Annexin A5 and FDG Uptake in ApoE-/-Mice

scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.

Contact Info

hi@scite.ai

10624 S. Eastern Ave., Ste. A-614

Henderson, NV 89052, USA

Product

Browser Extension Assistant by scite Citation Statement Search Reference Check Visualizations Dashboards Explore Journals Explore Organizations Explore Funders Embedding Badge Embedding Citation Search Pricing

Resources

Blog Help & FAQ Accessibility Statement API Terms For Universities & Governments For Researchers For Publishers For Corporate, Pharma & Enterprise Author Marketing Become an Affiliate Get an organization trial or quote scite Data & Services

About

News & Press Careers Read our Paper Coverage

Blog Terms and Conditions API Terms Privacy Policy Contact Cookie Preferences Do Not Sell or Share My Personal Information

Copyright © 2024 scite LLC. All rights reserved.

Made with 💙 for researchers

Part of the Research Solutions Family.