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Characterization of A Hypertriglyceridemic Transgenic Miniature swine Model expressing Human Apolipoprotein CIII.
MedLine Citation:
PMID:  22023023     Owner:  NLM     Status:  Publisher    
Abstract/OtherAbstract:
Hypertriglyceridemia was recently considered to be an independent risk factor for coronary heart disease (CHD), in which apolipoprotein CIII (ApoCIII) is one of the major contributing factors, as it is strongly correlated with plasma triglyceride levels. Although ApoCIII transgenic mice had been generated as an animal model for the study of hypertriglyceridemia, the features of lipoprotein metabolism in mice differ greatly from that of humans. Due to the high similarity between swine and humans with respect to lipid metabolism and cardiovascular physiology, we generated transgenic miniature swine expressing human ApoCIII through the transfection of somatic cells combined with nuclear transfer. The expression of human ApoCIII was detected in the liver and intestine of the transgenic pigs. Compared with non-transgenic controls, transgenic pigs showed significantly increased plasma triglyceride levels (83±36 vs 38±4 mg/dl, p<0.01) when fed a chow diet. Plasma lipoprotein profiling by FPLC in transgenic animals showed a higher peak at large particle fractions corresponding to VLDL (very low density lipoprotein)/Chylomicrons when triglyceride content in the fractions was assayed. There was not much difference in cholesterol content in FPLC fractions although a big LDL(low density lipoprotein)peak was identified in both non-transgenic and transgenic animals, which resembles to that of humans. Further analysis revealed markedly delayed clearance of plasma triglyceride accompanied with significantly reduced LPL (lipoprotein lipase) activity in post-heparin plasma in transgenic pigs, compared with non-transgenic controls. In summary, we have successfully generated a novel hypertriglyceridemic ApoCIII transgenic miniature swine model, which could be of great value for studies on hyperlipidemia in relation with atherosclerotic disorders.
Authors:
Jingyuan Wei; Hongsheng Ouyang; Yuhui Wang; Daxin Pang; Nathan X Cong; Tiedong Wang; Bingfeng Leng; Dong Li; Xiaoping Li; Rong Wu; Yu Ding; Fei Gao; Yanhong Deng; Bo Liu; Ziyi Li; Liangxue Lai; Haihua Feng; George Liu; Xuming Deng
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Publication Detail:
Type:  JOURNAL ARTICLE     Date:  2011-10-24
Journal Detail:
Title:  The FEBS journal     Volume:  -     ISSN:  1742-4658     ISO Abbreviation:  -     Publication Date:  2011 Oct 
Date Detail:
Created Date:  2011-10-25     Completed Date:  -     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  101229646     Medline TA:  FEBS J     Country:  -    
Other Details:
Languages:  ENG     Pagination:  -     Citation Subset:  -    
Copyright Information:
Journal compilation © 2011 Federation of European Biochemical Societies.
Affiliation:
Laboratory Animal Center, Jilin University, Changchun, 130062, P.R. China. College of Animal Science and Veterinary Medicine, Jilin University, Changchun, 130062, P.R. China. Institute of Zoonesis, Jilin University, Changchun, 130062, P.R. China. Jilin Provincial Key Laboratory of Animal Embryo Engineering, Changchun, 130062, P.R. China. Institute of Cardiovascular Science, Peking University Health Science Center, Beijing, 100069, P.R. China. Liaoning Province Academy of Analytic Science,Shenyang 110015, P.R. China. The Center for Animal Embryo Engineering of Jilin Province,Changchun, 130062, P.R. China.
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