Evaluation of Atherosclerosis Development by Vascular Duplex Ultrasonography in ApoE-deficient Dogs Fed with a High-fat Diet

Lingyun Jia, MD, PhD; Yuan Li, PhD; Yang Hua, MD; Yumei Liu, MD; Nan Zhang, MD; Mingjie Gao, MD; Ke Zhang, MD; Jingzhi Li, MD; Benchi Chen, BS; Jidong Mi, MS; Nan Zhao, PhD

doi:10.37015/AUDT.2024.230037

ADVANCED ULTRASOUND IN DIAGNOSIS AND THERAPY >

2024 , Vol. 8 >Issue 2: 49 - 56

DOI: https://doi.org/10.37015/AUDT.2024.230037

Original Research

Evaluation of Atherosclerosis Development by Vascular Duplex Ultrasonography in ApoE-deficient Dogs Fed with a High-fat Diet

Lingyun Jia, MD, PhD ,
Yuan Li, PhD ,
Yang Hua, MD ,
Yumei Liu, MD ,
Nan Zhang, MD ,
Mingjie Gao, MD ,
Ke Zhang, MD ,
Jingzhi Li, MD ,
Benchi Chen, BS ,
Jidong Mi, MS ,
Nan Zhao, PhD

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^aDepartment of Vascular Ultrasonography, Xuanwu Hospital, Capital Medical University
^bBeijing Diagnostic Center of Vascular Ultrasound
^cCenter of Vascular Ultrasonography, Beijing Institute of Brain Disorders, Collaborative Innovation Center for Brain Disorders, Capital Medical University, Beijing, China
^dBeijing Sinogene Biotechnology Co. Ltd, Beijing, China
^eDepartment of Physiology and Pathophysiology, School of Basic Medical Science, Capital Medical University, Beijing, China

¹ Lingyun Jia and Yuan Li contributed equally to this study.

No. 45 Changchun Road, Xuanwu Hospital, Beijing 100053, China，e-mail: dryanghua99@163.com

Received date: 2023-08-18

Accepted date: 2024-03-27

Online published: 2024-07-01

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Abstract

Objective This study aimed to evaluate the development of atherosclerosis in ApoE-deficient dogs fed with a high-fat diet (HFD) using vascular duplex ultrasonography (VDU).

Methods Thirty beagle dogs were enrolled, including 10 wild-type, 16 heterozygous (ApoE^-/+), and four homozygous (ApoE^-/-) mutant dogs. The dogs were categorized into either the normal diet (ND) or HFD group. Plasma lipids levles were tested at baseline and then after feeding the dog a different diet for 6 months. The carotid arteries, abdominal aorta (AO) and iliac arteries were examined using VDU. Artery sections of the ApoE^-/- dogs were analyzed.

Results After HFD, lipids especially triglycerides, total cholesterol and low-density lipoprotein (LDL) in the wild type and ApoE^-/+ dogs were significantly increased. Both the intima-media thickness (IMT) of the common carotid artery (CCA) and AO in the wild type and ApoE^-/+ dogs significantly increased. In the ApoE^-/+ dogs, the mean percentages increases in CCA-IMT and AO-IMT after HFD were higher than those in the ND dogs. The mean values of CCA-IMT and AO-IMT in the ApoE^-/-dogs increased to 2-2.5 folds after HFD. Histological analysis confirmed that the carotid and iliac arteries had advanced atherosclerotic lesions in the ApoE^-/- dogs.

Conclusions HFD may accelerate the development of atherosclerosis in ApoE-deficient dogs, which is an optimal large-animal model of atherosclerosis.

Key words： Atherosclerosis; ApoE-deficient dogs; Animal model; High-fat diet; Ultrasound

Cite this article

Lingyun Jia, MD, PhD , Yuan Li, PhD , Yang Hua, MD , Yumei Liu, MD , Nan Zhang, MD , Mingjie Gao, MD , Ke Zhang, MD , Jingzhi Li, MD , Benchi Chen, BS , Jidong Mi, MS , Nan Zhao, PhD . Evaluation of Atherosclerosis Development by Vascular Duplex Ultrasonography in ApoE-deficient Dogs Fed with a High-fat Diet[J]. ADVANCED ULTRASOUND IN DIAGNOSIS AND THERAPY, 2024 , 8(2) : 49 -56 . DOI: 10.37015/AUDT.2024.230037

References

[1]	Libby P, Ridker PM, Hansson GK. Progress and challenges in translating the biology of atherosclerosis. Nature 2011; 473:317-325.
[2]	Emini Veseli B, Perrotta P, De Meyer GRA, Roth L, Van der Donckt C, Martinet W, et al. Animal models of atherosclerosis. Eur J Pharmacol 2017; 816:3-13.
[3]	Feng C, Wang X, Shi H, Yan Q, Zheng M, Li J, et al. Generation of ApoE deficient dogs via combination of embryo injection of CRISPR/Cas9 with somatic cell nuclear transfer. J Genet Genomics 2018; 45:47-50.
[4]	Jia LY, Li Y, Hua Y, Liu YM, Zhang N, Gao MJ, et al. Identification of the atherosclerosis phenotype in vivo by vascular duplex ultrasonography in ApoE-deficient dogs. Atherosclerosis Plus 2022; 47:8-15.
[5]	Plump AS, Smith JD, Hayek T, Aalto-Set?l? K, Walsh A, Verstuyft JG, et al. Severe hypercholesterolemia and atherosclerosis in apolipoprotein E-deficient mice created by homologous recombination in ES cells. Cell 1992; 71:343-353.
[6]	Ishibashi S, Goldstein JL, Brown MS, Herz J, Burns DK. Massive xanthomatosis and atherosclerosis in cholesterol-fed low density lipoprotein receptor-negative mice. J Clin Invest 1994; 93:1885-1893.
[7]	Touboul PJ, Hennerici MG, Meairs S, Adams H, Amarenco P, Bornstein N, et al. Mannheim carotid intima-media thickness and plaque consensus (2004-2006-2011). An update on behalf of the advisory board of the 3rd, 4th and 5th watching the risk symposia, at the 13th, 15th and 20th European Stroke Conferences, Mannheim, Germany, 2004, Brussels, Belgium, 2006, and Hamburg, Germany, 2011. Cerebrovasc Dis 2012; 34:290-296.
[8]	Fang B, Ren X, Wang Y, Li Z, Zhao L, Zhang M, et al. Apolipoprotein E deficiency accelerates atherosclerosis development in miniature pig. Dis Model Mech 2018:11dmm036632.
[9]	Maldonado EN, Romero JR, Ochoa B, Aveldano MI. Lipid and fatty acid composition of canine lipoproteins. Comp Biochem Physiol B Biochem Mol Biol 2001; 128:719-729.
[10]	Zhao H, Zhao J, Wu D, Sun Z, Hua Y, Zheng M, et al. Dogs lacking Apolipoprotein E show advanced atherosclerosis leading to apparent clinical complications. Sci China Life Sci 2022; 65:1342-1356.
[11]	Shi XF, Zhu SM, Liu MJ, Stone SS, Rong Y, Mao K, et al.. Single-cell RNA-Seq reveals a population of smooth muscle cells responsible for atherogenesis. Aging and disease 2022; 13:1939-1953.
[12]	Getz GS, Reardon CA. Animal models of atherosclerosis. Arterioscler Thromb Vasc Biol 2012; 32:1104-1115.
[13]	Shim J, Al-Mashhadi RH, S?rensen CB, Bentzon JF. Large animal models of atherosclerosis - new tools for persistent problems in cardiovascular medicine. J Pathol 2016; 238:257-266.
[14]	Fan JL, Chen YJ, Yan HZ, Niimi M, Wang YL, Liang JY. Principles and applications of rabbit models for atherosclerosis. J Atheroscler Thromb 2018; 25:213-220.
[15]	Herrmann AM., Meckel S., Gounis MJ., Kringe L., Motschall E., Mulling C, et al. Large animals in neurointerventional research: A systematic review on models, techniques and their application in endovascular procedures for stroke, aneurysms and vascular malformations. J Cereb Blood Flow Metab 2019; 39:375-394.

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