Novel microminipig model of atherosclerosis by high fat and high cholesterol diet, established in Japan.
Novel atherosclerotic lesions were induced in the Microminipig (MMP, registered with the Japanese Ministry of Agriculture, Forestry and Fisheries as a novel variety of swine), the smallest pig available for experimental use, by feeding a high fat (12%) and high cholesterol (5%) diet (HFCD) with sodium cholate (SC, 0.7%) (HFCD/SC) for three months. Three MMPs were used: a male fed with normal diet (M-ND), and a male and an ovariectomized female fed with HFCD/SC (M-HFCD/SC and Fx-HFCD/SC). HFCD/SC induced hypercholesterolemia accompanied by an increase in serum total cholesterol (T-Cho), low-density lipoprotein cholesterol (LDL-C), high-density lipoprotein cholesterol (HDL-C) and cholesterol ester (CE) from the first week. Serum levels of T-Cho, LDL-C and CE reached a maximum in two to three weeks, and HDL-C gradually increased during the experimental period (duration). Serum lipoprotein analysis showed a dominant LDL-C fraction, as seen in humans, in all three MMPs. Body weight gain in the MMPs fed with HFCD/SC was greater than in the animal fed with M-ND. At the end of the experiment, computed tomography scans of conscious animals showed increases in subcutaneous and abdominal fat in those fed with HFCD/SC, suggesting the induction of obesity. Atherosclerotic lesions in systemic arteries (including external and internal iliac arteries, abdominal aorta, coronary artery, cerebral arterial circle), fatty changes, and foamy cell infiltration in the liver and spleen were histopathologically observed in the MMPs fed with HFCD/SC. Atherosclerosis and the pathological findings induced by HFCD/SC in MMPs were similar to the pathological changes associated with human atherosclerosis, suggesting that the MMP has the potential to be a suitable animal model for human atherosclerosis.
Department of Veterinary Pathology, Kagoshima University Graduate School of Medical and Dental Sciences, Kagoshima, Japan.
Noriaki
N
Miyoshi
Masahisa
M
Horiuchi
Yoshinori
Y
Inokuchi
Yoko
Y
Miyamoto
Naoki
N
Miura
Satatoshi
S
Tokunaga
Makoto
M
Fujiki
Yasukatsu
Y
Izumi
Hiroaki
H
Miyajima
Ryoichi
R
Nagata
Kazuhiro
K
Misumi
Toru
T
Takeuchi
Akihide
A
Tanimoto
Nobuhiro
N
Yasuda
Hiroki
H
Yoshida
Hiroaki
H
Kawaguchi
D000818:Animals; D001158:Arteries / Q000473:pathology; D050197:Atherosclerosis / Q000473:pathology* / Q000503:physiopathology*; D001835:Body Weight; D002788:Cholesterol Esters / Q000097:blood; D002791:Cholesterol, Dietary / Q000097:blood / Q000494:pharmacology*; D008076:Cholesterol, HDL / Q000097:blood; D008078:Cholesterol, LDL / Q000097:blood; D004195:Disease Models, Animal; D005260:Female; D006801:Humans; D006937:Hypercholesterolemia / Q000473:pathology / Q000503:physiopathology; D050152:Intra-Abdominal Fat / Q000000981:diagnostic imaging / Q000473:pathology; D007564:Japan; D008297:Male; D010052:Ovariectomy; D050151:Subcutaneous Fat / Q000000981:diagnostic imaging / Q000473:pathology; D013552:Swine; D013556:Swine, Miniature; D014057:Tomography, X-Ray Computed
D002788:Cholesterol Esters; D002791:Cholesterol, Dietary; D008076:Cholesterol, HDL; D008078:Cholesterol, LDL