title: Rapid development of atherosclerosis in the world's smallest Microminipig fed a high-fat/high-cholesterol diet.
abstract: OBJECTIVE
  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 Microminipig(TM).
  
  
  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.
  
  
  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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Laboratory of Veterinary Histopathology, Joint Faculty of Veterinary Medicine, Kagoshima University.
authors.forename: Hiroaki
authors.initials: H
authors.lastname: Kawaguchi
authors.forename: Tomonobu
authors.initials: T
authors.lastname: Yamada
authors.forename: Naoki
authors.initials: N
authors.lastname: Miura
authors.forename: Makoto
authors.initials: M
authors.lastname: Ayaori
authors.forename: Harumi
authors.initials: H
authors.lastname: Uto-Kondo
authors.forename: Masaya
authors.initials: M
authors.lastname: Ikegawa
authors.forename: Michiko
authors.initials: M
authors.lastname: Noguchi
authors.forename: Ke-Yong
authors.initials: KY
authors.lastname: Wang
authors.forename: Hiroyuki
authors.initials: H
authors.lastname: Izumi
authors.forename: Akihide
authors.initials: A
authors.lastname: Tanimoto
mesh_terms: D000071479:APOBEC-1 Deaminase; D050154:Adiposity; D000818:Animals; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology*; D001794:Blood Pressure; D001835:Body Weight; D053480:Cholesterol Ester Transfer Proteins / Q000378:metabolism; D002791:Cholesterol, Dietary / Q000008:administration & dosage*; D003564:Cytidine Deaminase / Q000235:genetics; D059305:Diet, High-Fat; D004195:Disease Models, Animal; D008049:Lipase / Q000378:metabolism; D008074:Lipoproteins / Q000097:blood; D008297:Male; D012333:RNA, Messenger / Q000235:genetics; D020133:Reverse Transcriptase Polymerase Chain Reaction; D013552:Swine; D013556:Swine, Miniature
chemical_list: D053480:Cholesterol Ester Transfer Proteins; D002791:Cholesterol, Dietary; D008074:Lipoproteins; D012333:RNA, Messenger; D008049:Lipase; D000071479:APOBEC-1 Deaminase; C000605089:APOBEC1 protein, human; C000605090:Apobec1 protein, mouse; D003564:Cytidine Deaminase