IMR Press / FBL / Volume 28 / Issue 4 / DOI: 10.31083/j.fbl2804070
Open Access Original Research
Evaluation on the Effectiveness of High Cholesterol Diet Feeding in Inducing Early and Established Atherosclerotic Lesions in New Zealand White Rabbits
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1 Institute of Pathology, Laboratory and Forensic Medicine (I-PPerForM), Universiti Teknologi MARA, 47000 Sungai Buloh, Selangor, Malaysia
2 Department of Pathology, Faculty of Medicine, Universiti Teknologi MARA, 47000 Sungai Buloh, Selangor, Malaysia
3 Department of Biochemistry & Molecular Medicine, Faculty of Medicine, Universiti Teknologi MARA, 47000 Sungai Buloh, Selangor, Malaysia
*Correspondence: noor202@uitm.edu.my (Noor Alicezah Mohd Kasim)
Front. Biosci. (Landmark Ed) 2023, 28(4), 70; https://doi.org/10.31083/j.fbl2804070
Submitted: 2 February 2023 | Revised: 6 March 2023 | Accepted: 21 March 2023 | Published: 6 April 2023
Copyright: © 2023 The Author(s). Published by IMR Press.
This is an open access article under the CC BY 4.0 license.
Abstract

Background: Various methods were used to induce atherosclerosis in rabbits. One of the most common methods used is high-cholesterol diet (HCD) feeding. However, the exact amount and duration of HCD feeding to induce early and established atherosclerosis in New Zealand white rabbits (NZWR) continue to be debated among researchers. Therefore, this study aims to evaluate the effectiveness of 1% HCD feeding in inducing early and established atherosclerosis lesions in NZWR. Methods: A total of 50 g/kg/day of 1% HCD was fed to three to four months old male rabbits weighing 1.8 to 2.0 kg for four and eight weeks to induce early and established atherosclerosis respectively. The body weight and lipid profile were measured at baseline and post-HCD intervention. Following euthanasia, the aorta was excised and prepared for histology and immunohistochemical analysis to confirm the stages of atherosclerosis. Results: The mean body weight of the rabbits in early and established atherosclerosis groups increased significantly up to 17.5% (p = 0.026) and 19.75% (p = 0.019) respectively compared to baseline. The total cholesterol level dramatically elevated up to 13-fold (p = 0.005) and 38-fold (p = 0.013) compared to baseline, after four and eight weeks of 1% HCD feeding respectively. The low-density lipoprotein level significantly increased up to 42-fold (p = 0.006) and 128-fold (p = 0.011) compared to baseline, after four and eight weeks of 1% HCD feeding respectively. Rabbits fed with four and eight weeks 1% HCD significantly developed 5.79% (p = 0.008) and 21.52% (p = 0.008) aortic lesion areas compared to the control group. Histological evaluation in the aorta showed accumulation of foam cells in early atherosclerosis group and formation of fibrous plaque and lipid core in the established atherosclerosis group. Rabbits fed with eight weeks HCD showed higher tissue expressions of ICAM-1, VCAM-1, e-selectin, IL-6, IL-8, NF-κBp65, and MMP-12 compared to four weeks of HCD intervention. Conclusions: A total of 50 g/kg/day of 1% HCD for four and eight weeks is sufficient to induce early and established atherosclerosis in NZWR respectively. The consistent results through this method could facilitate researchers in inducing early and established atherosclerosis in NZWR.

Keywords
cholesterol
rabbits
lipid profile
immunohistochemistry
atherosclerosis
Funding
600-IRMI/FRGS 5/3 (366/2019)/Ministry of Higher Education Malaysia
Figures
Fig. 1.
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