A novel swine model for evaluation of dyslipidemia and atherosclerosis induced by human CETP overexpression

Lipids in Health and Disease

Research

Jia-Qiang Wang¹  Zhong-Hua Liu¹  Tao Chen²  Bo Yu²  Meng Sun²  Jin-Jin Cui² 

[1] College of life science, Northeast Agricultural University of China, Harbin, China;The Key Laboratory of Myocardial Ischemia, Chinese Ministry of Education, Harbin, Heilongjiang, China;Cardiology Division, The Second Affiliated Hospital of Harbin Medical University, No. 246 Xuefu Road, 150086, Harbin, Heilongjiang, China;

关键词: Cholesteryl ester transfer protein;    Transgenic pig;    Atherosclerosis;    Metabolism;   

DOI  :  10.1186/s12944-017-0563-x

 received in 2017-07-03, accepted in 2017-09-04,  发布年份 2017

来源: Springer

【 摘 要 】

BackgroundThe mechanism of cholesteryl ester transfer protein (CETP) in lipid metabolism is still unclear. Furthermore, the relationship of CETP and atherosclerosis (AS) has been controversial. As pigs are a good model for both lipid and AS research, we investigated the lipid metabolism of human CETP (hCETP) transgenic pigs and explored the mechanism of CETP in lipid modulation.MethodsPlasmids expressing the hCETP gene were designed, successfully constructed, and transfected into porcine fetal fibroblasts by liposomes. Using somatic cell nuclear transfer technology and embryonic transfer, hCETP transgenic pigs were generated. After the DNA, RNA, and protein levels were identified, positive hCETP transgenic pigs were selected. Blood samples were collected at different ages to evaluate the phenotypes of biochemical markers, and the metabolomes of plasma samples were analyzed by liquid mass spectrometry.ResultsEight positive hCETP transgenic pigs and five negative cloned pigs were generated by transgenic technology. Finally, five hCETP transgenic and five cloned pigs were grown healthily. After feeding with a normal diet, hCETP transgenic pigs compared with unmodified pigs had no significant differences in body weight, liver function, kidney function, or plasma ions, while total cholesterol and low-density lipoprotein were higher than in unmodified pigs, and high-density lipoprotein was significantly decreased. Metabolomics analysis showed that there were differences in metabolic components between hCETP transgenic pigs, cloned pigs, and unmodified pigs.ConclusionsIn this study, we created hCETP transgenic pigs that could serve as an excellent model for lipid disorders and atherosclerosis.

【 授权许可】

CC BY   
© The Author(s). 2017