Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
Randomized Controlled Trial
. 2012:2012:249129.
doi: 10.1155/2012/249129. Epub 2012 Sep 4.

The immunologic injury composite with balloon injury leads to dyslipidemia: a robust rabbit model of human atherosclerosis and vulnerable plaque

Guangyin Zhang  1 , Ming Li, Liangjun Li, Yingzhi Xu, Peng Li, Cui Yang, Yanan Zhou, Junping Zhang
Affiliations
Randomized Controlled Trial

The immunologic injury composite with balloon injury leads to dyslipidemia: a robust rabbit model of human atherosclerosis and vulnerable plaque

Guangyin Zhang et al. J Biomed Biotechnol. 2012.

Abstract

Atherosclerosis is a condition in which a lipid deposition, thrombus formation, immune cell infiltration, and a chronic inflammatory response, but its systemic study has been hampered by the lack of suitable animal models, especially in herbalism fields. We have tried to perform a perfect animal model that completely replicates the stages of human atherosclerosis. This is the first combined study about the immunologic injury and balloon injury based on the cholesterol diet. In this study, we developed a modified protocol of the white rabbit model that could represent a novel approach to studying human atherosclerosis and vulnerable plaque.

PubMed Disclaimer

Figures

Figure 1
Figure 1
Schematic diagram of study timeline. Immunologic injury is followed by 2 weeks of high cholesterol feeding and balloon injury on week 4. *Means the times of serum collection and animal body weight.
Figure 2
Figure 2
Macroscopic observation of atherosclerotic plaques area and staining with Sudan III. (a) Macroscopic observation of the whole aorta. (b) Representative en face Sudan staining of the whole aorta. (c) Percentage of the atherosclerotic plaques area in both groups. The Ratio of atherosclerotic plaques area to the whole aorta was 54 ± 11% in CIB group, but no atherosclerotic plaques area has been detected in the normal group.
Figure 3
Figure 3
Histological examples of lipid core and the fibrous cap associated with rabbit atherosclerotic plaques. (a) A cross section of a normal rabbit aorta. (b) A cross section of a CIB rabbit atherosclerotic plaques. (c) Higher magnification of the atherosclerotic plaques site shows a thin fibrous cap. The fibrous cap thickness, (d) ratio of fibrous cap to intima media thickness (e), and vulnerability index (f) were calculated. Data are expressed as mean ± SD, **P < 0.01 compared with normal.
Figure 4
Figure 4
Vulnerability plaque has been identified on CIB rabbit. (a) Representative aortic sections stained by Oil red O, trichrome, CD68 antibody and a SMC-specific antibody (magnification ×40). (b) Quantification revealed a significantly larger lipid core, collagen, SMA-positive area, and the density of macrophages (identified by CD 68 immunostaining) in CIB rabbits. Data are expressed as mean ± SD, **P < 0.01 compared with normal.
Figure 5
Figure 5
Representative hematoxylin-eosin staining for intima/medial thickness of aortic arch, thoracic aorta, and abdominal aorta (magnification ×40). The pathology of the abdominal aortic was most serious, followed by the thoracic aorta and aortic arch. Data are expressed as mean ± SD, *P < 0.01, **P < 0.01 compared with normal group.
Figure 6
Figure 6
Representative immunohistochemical staining for MMP-9, NF-κB P65 subunit, CD31 and VEGF. Strong positive staining was observed in CIB group and weak staining on the sections of arteries from normal group. MMP-9, matrix metalloproteinase-9; NF-κB P65 subunit, nuclear factor-κB P65 subunit; CD31, cluster of differentiation 31; VEGF, vascular endothelial growth factor. Data are expressed as mean ± SD, **P < 0.01 compared with normal.
Figure 7
Figure 7
Analysis of biochemical measurements in two groups of rabbits. Serum level of IL-1, ox-LDL, NO, SOD, MDA, MCP-1, and TNF-α by using of enzyme-linked immunosorbent assay on week 0, 3, 6, 10. IL-1, interleukin-1; ox-LDL, oxidized LDL cholesterol; NO, nitric oxide; SOD, superoxide dismutase; MDA, malondialdehyde; MCP-1, monocyte chemoattractant protein-1; TNF-α, tumor necrosis factor-α. Data are expressed as mean ± SD, *P < 0.05, **P < 0.01 compared with normal group.
See this image and copyright information in PMC

Similar articles

See all similar articles

Cited by

References

    1. Galkina E, Ley K. Immune and inflammatory mechanisms of atherosclerosis. Annual Review of Immunology. 2009;27:165–197. - PMC - PubMed
    1. Doran AC, Meller N, McNamara CA. Role of smooth muscle cells in the initiation and early progression of atherosclerosis. Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28(5):812–819. - PMC - PubMed
    1. Vinegoni C, Botnaru I, Aikawa E, et al. Indocyanine green enables near-infrared fluorescence imaging of lipid-rich, inflamed atherosclerotic plaques. Science Translational Medicine. 2011;3(84)84ra45 - PMC - PubMed
    1. Ross R. Atherosclerosis—an inflammatory disease. The New England Journal of Medicine. 1999;340(2):115–126. - PubMed
    1. Hansson GK, Libby P. The immune response in atherosclerosis: a double-edged sword. Nature Reviews Immunology. 2006;6(7):508–519. - PubMed

Publication types