title: Morphological features of coronary plaques in WHHLMI rabbits (Oryctolagus cuniculus), an animal model for familial hypercholesterolemia.
abstract: In order to examine their suitability for studies on coronary atherosclerosis, we evaluated the features of coronary atherosclerotic plaques in myocardial infarction-prone Watanabe heritable hyperlipidemic (WHHLMI) rabbits, a spontaneous animal model for coronary atherosclerosis and myocardial infarction. Coronary segments of the hearts of 187 WHHLMI rabbits (10-29 months old) were sectioned serially and stained histopathologically and immunohistologically. Progression of coronary lesions was prominent in rabbits that had died suddenly. The degree of coronary lesions of females was higher than that of males. Various types of atherosclerotic lesions were observed in the coronary arteries, such as plaques with a large lipid core covered by a thin fibrous cap, fatty streaks, early and advanced fibroatheromas, fibrous lesions, and advanced lesions with calcium accumulation and the vasa vasorum. In rabbits that had died suddenly, the frequencies of fibroatheromas or advanced lesions were higher than those of rabbits euthanized. Matrix metalloproteinase (MMP)-positive macrophages were detected in gaps among endothelial cells at the plaque surface, beneath the fibrous cap of thin-capped fibroatheromas, and at the bottom of the intimal plaques in which the tunica media was attenuated. Immunohistological results suggest that MMP-positive macrophages are involved in the initiation, progression, and destabilization of coronary plaques, in addition to vascular remodeling, even in WHHLMI rabbits. In conclusion, coronary lesions in WHHLMI rabbits resemble human atherosclerotic lesions, and thus, the WHHLMI rabbit is a suitable animal model for studies on human coronary plaques.
authors.affiliation: Institute for Experimental Animals, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Satoshi
authors.initials: S
authors.lastname: Yamada
authors.affiliation: Institute for Experimental Animals, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Tomonari
authors.initials: T
authors.lastname: Koike
authors.affiliation: Division of Comparative Pathophysiology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Takayuki
authors.initials: T
authors.lastname: Nakagawa
authors.affiliation: Institute for Experimental Animals, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Nobue
authors.initials: N
authors.lastname: Kuniyoshi
authors.affiliation: Institute for Experimental Animals, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.
authors.forename: Yu
authors.initials: Y
authors.lastname: Ying
authors.affiliation: Division of Biological Chemistry, Department of Molecular Biology, Showa University School of Pharmacy, 1-5-8 Hatanodai, Shinagawa, Tokyo 142-8555, Japan.
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Itabe
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Atsushi
authors.initials: A
authors.lastname: Yamashita
authors.affiliation: Department of Pathology, Faculty of Medicine, University of Miyazaki, 5200 Kihara, Kiyotake, Miyazaki 889-1692, Japan.
authors.forename: Yuji
authors.initials: Y
authors.lastname: Asada
authors.affiliation: Institute for Experimental Animals, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe, Hyogo 650-0017, Japan.|Division of Comparative Pathophysiology, Department of Physiology and Cell Biology, Kobe University Graduate School of Medicine, 7-5-1 Kusunoki-cho, Chuo-ku, Kobe 650-0017, Japan.
authors.forename: Masashi
authors.initials: M
authors.lastname: Shiomi
mesh_terms: D000818:Animals; D003324:Coronary Artery Disease / Q000473:pathology*; D003331:Coronary Vessels / Q000473:pathology*; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006938:Hyperlipoproteinemia Type II / Q000473:pathology*; D008264:Macrophages / Q000201:enzymology / Q000473:pathology; D008297:Male; D020782:Matrix Metalloproteinases / Q000378:metabolism; D058226:Plaque, Atherosclerotic / Q000473:pathology*; D011817:Rabbits; D017540:Tunica Media / Q000473:pathology
chemical_list: D020782:Matrix Metalloproteinases
keywords: MMP-positive macrophages; WHHLMI rabbit; animal model; coronary atherosclerosis