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A Novel Porcine Model of Atherosclerosis
Author(s) -
Mazur Meredith J.,
Zachary James F.,
Pettigrew James E.,
Schook Lawrence B.
Publication year - 2006
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.20.4.a207
Subject(s) - oil red o , cholesterol , regimen , medicine , biology , pcsk9 , arteriosclerosis , endocrinology , clone (java method) , lipoprotein , ldl receptor , biochemistry , gene , adipose tissue , adipogenesis
We are investigating the potential use of the pig as a model for the study of atherosclerosis by utilizing APOE sequence information, animal cloning, and establishing a nutritional regimen that temporally enhances the formation of atheromas. Analysis of sequencing data revealed Duroc 2–14 was homozygous for the ApoE4 allele, which is responsible for an increased risk of developing atherosclerosis in humans. Duroc 2–14 fetal fibroblasts were used to clone pigs via nuclear transfer and four pigs were chosen to participate in a nutritional feeding regimen to study the formation of atheromas. Pigs were randomly assigned to one of two treatment groups, n = 2 in control diet (CD); n = 2 in high‐fat, high‐cholesterol diet (HFHC) for a 60 day feeding trial. Blood samples were collected six months prior to initiation of the trial to establish baseline lipoprotein profiles and collected for lipoprotein analysis at 0, 2, 4, and 8.5 weeks during the trial. After 60 days, aortas were collected and analyzed for fatty streaks. The HFHC diet induced a five‐fold increase in total plasma cholesterol concentration and an eight‐fold increase in plasma LDL cholesterol concentration. Sudan IV staining of the intimal surfaces of the aortas from pigs fed the HFHC diet revealed fatty streaks and Oil Red‐O stain confirms subendothelial deposits of lipid in the aortas.