Variation in susceptibility to atherosclerosis among inbred strains of mice

Paigen, Beverly; Morrow, Arlene; Brandon, Catherine; Mitchell, Diane C.; Holmes, Patricia A.

doi:10.1016/0021-9150(85)90138-8

Cited by 563 publications

(404 citation statements)

References 15 publications

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“…While the IL‐33 −/− mouse line was originally backcrossed for more than 10 generations into the C57BL/6 background, the backcross of the ST2 −/− mouse line is less complete with remnants of genetic material from the original 129 mouse strain 18. Of note, ApoE −/− mice in a 129 background have smaller lesions in the aortic roots 23 and the aorta 24 than ApoE −/− mice in a C57BL/6 background. Another possibility could be that ST2 has other ligands than IL‐33 or that IL‐33 has unique intracellular activities independent of ST2.…”

Section: Resultsmentioning

confidence: 99%

Atherosclerosis severity is not affected by a deficiency in IL‐33/ST2 signaling

Martin

Palmer

Rodriguez

et al. 2015

Immunity Inflam & Disease

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Interleukin (IL)‐33 is a cytokine of the IL‐1 family, which signals through the ST2 receptor. Previous work demonstrated that the systemic administration of recombinant IL‐33 reduces the development of atherosclerosis in apolipoprotein E‐deficient (ApoE−/−) mice by inducing a Th1‐to‐Th2 shift. The objective of our study was to examine the role of endogenous IL‐33 and ST2 in atherosclerosis. ApoE−/−, IL‐33−/−ApoE−/−, and ST2−/−ApoE−/− mice were fed with a cholesterol‐rich diet for 10 weeks. Additionally, a group of ApoE−/− mice was injected with a neutralizing anti‐ST2 or an isotype control antibody during the period of the cholesterol‐rich diet. Atherosclerotic lesion development was measured by Oil Red O staining in the thoracic‐abdominal aorta and the aortic sinus. There were no significant differences in the lipid‐staining area of IL‐33−/−ApoE−/−, ST2−/−ApoE−/−, or anti‐ST2 antibody‐treated ApoE−/− mice, compared to ApoE−/− controls. The absence of IL‐33 signaling had no major and consistent impact on the Th1/Th2 cytokine responses in the supernatant of in vitro‐stimulated lymph node cells. In summary, deficiency of the endogenously produced IL‐33 and its receptor ST2 does not impact the development of atherosclerosis in ApoE‐deficient mice.

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Section: Resultsmentioning

confidence: 99%

Atherosclerosis severity is not affected by a deficiency in IL‐33/ST2 signaling

Martin

Palmer

Rodriguez

et al. 2015

Immunity Inflam & Disease

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“…Paigen et al (16) showed that an atherogenic diet (15% fat, 1% cholesterol and 0.5% cholic acid) induces atherosclerotic lesions at the aortic roots in wildtype mice, and that 129 mice are mildly resistant while C57BL/6 mice are susceptible to this diet-induced atherosclerosis. In agreement with this, we find that the plaques at the aortic root area of 4-6 month old 129-apoE mice are significantly smaller than in B6-apoE mice as shown in table 1 despite the mean age of 5.4 mo in this group of 129-apoE was older than 4.3 mo in B6-apoE.…”

Section: Atherosclerosis At Aortic Rootmentioning

confidence: 99%

Anatomical differences and atherosclerosis in apolipoprotein E-deficient mice with 129/SvEv and C57BL/6 genetic backgrounds

et al. 2007

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There are well-known genetic background effects on atherosclerosis susceptibility in mice. To study the basis of these effects, we have generated the apolipoprotein E-null mutation in mouse embryonic stem cells of 129/SvEv origin, maintained it in the inbred strain (129-apoE), and compared these mice with those previously made in strain 129/Ola and backcrossed to a C57BL/6 genetic background (B6-apoE). Plasma cholesterol and triglyceride levels in the apoE-129 mice are twice the levels in apoE-B6, and both VLDL/chylomicron remnants and HDL particles are increased. Regression analysis of plaque size relative to the age of mice suggests that the initiation of atherosclerotic plaque development at the aortic root is slower in 129-apoE mice (intercept at 3.9 mo in females and 4.1 mo in males) than in B6-apoE mice (1.3 mo in females and 2.8 mo in males). In contrast, 129-apoE mice develop extensive plaques in the aortic arches earlier than B6-apoE mice. Distinct differences in the geometry of the aortic arch between the two strains suggest that anatomical differences may contribute to the effects of genetic background on atherosclerosis. The 129-apoE/B6-apoE pair thus provides a tool to study factors governing the relation between arterial geometry and the location of plaque development. Keywordsanimal model; atherosclerotic plaque distribution; cholesterol; aortic arch; aortic root; inbred mouse strain; ductus arteriosus Well-characterized animal models are essential for the study of common human diseases such as those involving the cardiovascular system. The first practical mouse model of atherosclerosis was developed by inactivating the gene coding for apolipoprotein E (apoE) (1-3). ApoE plays a central role in lipoprotein metabolism and is required for efficient receptor-mediated plasma clearance by the liver of chylomicron remnants and very low-density lipoprotein (VLDL)-remnant particles (4). Lack of apoE in the mutant mice results in an increased accumulation of cholesterol-enriched remnant particles and four times normal plasma cholesterol levels even Correspondence to: Dr. Nobuyo Maeda, Department of Pathology and Laboratory Medicine, The University of North Carolina at Chapel Hill, 701 Brinkhous-Bullitt Building, Chapel Hill, NC 27599-7525. Phone: 919-966-6912, Fax: 919-966-8800. E-mail: nobuyo@med.unc.edu.. Publisher's Disclaimer: This is a PDF file of an unedited manuscript that has been accepted for publication. As a service to our customers we are providing this early version of the manuscript. The manuscript will undergo copyediting, typesetting, and review of the resulting proof before it is published in its final citable form. Please note that during the production process errors may be discovered which could affect the content, and all legal disclaimers that apply to the journal pertain. when the mice are fed regular low-fat, low-cholesterol chow. The apoE-deficient mice spontaneously develop atherosclerotic plaques similar to those seen in humans (5,6), with the exception that the spontaneo...

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“…Thus, by studying different inbred strains, they determined that genetic factors were involved in atherosclerosis susceptibility and altered plasma cholesterol levels in response to this atherogenic diet [12]. It was subsequently noted that both strains responded to the atherogenic diet by a decrease in their HDL cholesterol, but a greater HDL reduction was seen in the atherosclerosis susceptible C57BR/cdJ strain [13] Paigen and her colleagues found that this atherogenic diet was associated with morbid respiratory infections, and they modified it by blending it 1:3 with a 10% fat diet to achieve a diet containing 15% fat, 1.25% cholesterol, and 0.5% cholate [14,15], a diet widely used today, and referred to by many researchers as the 'Paigen diet.' This diet still contains extremely high amounts of cholesterol compared to human diets (0.05-0.15%) or normal mouse chow (0.02%), and high levels of sodium cholate, which is also nonphysiological.…”

Section: Diet-induced Atherosclerosismentioning

confidence: 99%

“…Paigen's laboratory characterized aortic root lesions in 10 inbred strains fed this diet for 14 weeks. Five of the strains failed to develop lesions (BALB/CJ, C3H/J, A/J, SWR/J, and NZB/J), whilst five developed differing numbers of lesions (C57BL/6J Ͼ C57/LJ Ͼ DBA/ 2J ϭ AKR/J ϭ 129/J) [15]. The inbred strains had variable total plasma cholesterol values in response to this diet; however, there was no correlation in these inbred strains between total plasma cholesterol and lesion susceptibility [15].…”

Section: Diet-induced Atherosclerosismentioning

confidence: 99%

The emergence of mouse models of atherosclerosis and their relevance to clinical research

Smith

Breslow

1997

Journal of Internal Medicine

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Due to the ability to introduce or mutate genes, the mouse has become the most common experimental animal model for atherosclerosis research. Wildtype mice on a chow diet do not get atherosclerosis. Three ways to induce atherosclerosis in mice are discussed: diet-induced, apoE deficiency-induced, and LDL receptor-deficiency induced. The atherosclerotic lesions in apoE-deficient mice have been well characterized, and they resemble human lesions in their sites of predilection and progression to the fibroproliferative stage. These mouse models of atherosclerosis are being used to identify genes which modify atherosclerosis susceptibility and in the development of antiatherogenic therapies.

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Variation in susceptibility to atherosclerosis among inbred strains of mice

Cited by 563 publications

References 15 publications

Atherosclerosis severity is not affected by a deficiency in IL‐33/ST2 signaling

Atherosclerosis severity is not affected by a deficiency in IL‐33/ST2 signaling

Anatomical differences and atherosclerosis in apolipoprotein E-deficient mice with 129/SvEv and C57BL/6 genetic backgrounds

The emergence of mouse models of atherosclerosis and their relevance to clinical research

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