Rapid development of atherosclerosis in the world's smallest microminipig fed a high-fat/high-cholesterol diet a useful animal model due to its size and similarity to human pathophysiology
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- Kawaguchi Hiroaki
- Laboratory of Veterinary Histopathology, Joint Faculty of Veterinary Medicine, Kagoshima University
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- Yamada Tomonobu
- Shin Nippon Biomedical Laboratories, Ltd. Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health
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- Miura Naoki
- Veterinary Teaching Hospital, Joint Faculty of Veterinary Medicine, Kagoshima University
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- Ayaori Makoto
- Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College
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- Uto-Kondo Harumi
- Division of Anti-aging and Vascular Medicine, Department of Internal Medicine, National Defense Medical College
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- Ikegawa Masaya
- Department of Genomic Medical Sciences, Kyoto Prefectural University of Medicine, Graduate School of Medical Science
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- Noguchi Michiko
- Laboratory of Domestic Animal Internal Medicine, Joint Faculty of Veterinary Medicine, Kagoshima University
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- Wang Ke-Yong
- Department of Pathology and Cell Biology, School of Medicine, University of Occupational and Environmental Health
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- Izumi Hiroyuki
- Shin Nippon Biomedical Laboratories, Ltd.
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- Tanimoto Akihide
- Department of Molecular and Cellular Pathology, Kagoshima University Graduate School of Medical and Dental Sciences
書誌事項
- タイトル別名
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- Rapid Development of Atherosclerosis in the World’s Smallest Microminipig Fed a High-Fat/High-Cholesterol Diet
- A Useful Animal Model Due to its Size and Similarity to Human Pathophysiology
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説明
Aim: Experimental studies of human atherogenesis require an appropriate animal model that mimics human physiology and pathology. Because swine physiology is similar to human physiology, we developed a hyperlipidemia-induced atherosclerosis model using the recently developed world’s smallest MicrominipigTM.<br> Methods: These animals weigh only 5kg at 3months of age, much smaller than any other miniature pig. We found that the administration of a high-fat/high-cholesterol diet containing at least 0.2% cholesterol without cholic acid for as little as eight weeks induces hypercholesterolemia and subsequent atherosclerosis in these animals.<br> Results: The serum levels of low-density lipoprotein cholesterol(LDL-C) and the percent distribution of cholesterol in the LDL fractions were markedly increased. The hepatic expression of LDL receptor and hydroxymethylglutaryl-CoA reductase was coordinately decreased. The cholesteryl ester transfer protein activity, which plays a role in reverse cholesterol transport, was detected in the serum of the Microminipigs. Niemann-Pick C1-like 1 protein was expressed in both the liver and small intestine; however, hepatic apoB mRNA editing enzyme was not expressed. As in humans, and in contrast to that observed in mice, most of the hepatic lipase activity was localized in the liver. These results suggest that the hyperlipidemia-induced gene expression profile linked to cholesterol homeostasis and atherogenesis is similar in Microminipigs and humans.<br> Conclusion: We conclude that the characteristics of the Microminipig, including its easy handling size, make it an appropriate model for studies of atherosclerosis and related conditions.
収録刊行物
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- Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ
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Ｊｏｕｒｎａｌ ｏｆ Ａｔｈｅｒｏｓｃｌｅｒｏｓｉｓ ａｎｄ Ｔｈｒｏｍｂｏｓｉｓ 21 (3), 186-203, 2014
一般社団法人 日本動脈硬化学会