Improving lipoprotein profiles by liver-directed gene transfer of low density lipoprotein receptor gene in hypercholesterolaemia mice

Journal of genetics

HAILONG OU1²  QINGHAI ZHANG¹  JIA ZENG² 

[1] Department of Biology, Guizhou Medical University, Guiyang, Guizhou 550004, People’s Republic of China$$;Department of Biochemistry and Molecular Biology, uiyang, Guizhou 550004, People’s Republic of China$$

关键词: low density lipoprotein receptor;    familial hypercholesterolemia;    gene therapy;    atherosclerosis;    lipid metabolism;   

DOI  :  

学科分类：生物科学（综合）

来源: Indian Academy of Sciences

【 摘 要 】

The defect of low density lipoprotein receptor disturbs cholesterol metabolism and causes familial hypercholesterolaemia(FH). In this study, we directly delivered exogenousLdlrgene into the liver of FH model mice (Ldlr−/−) by lentiviral genetransfer system. The results showed that theLdlrgene controlled by hepatocyte-specific human thyroxine-binding globulin(TBG) promoter successfully and exclusively expressed in livers. We found that, although, the content of high density lipopro-tein in serum was not significantly affected by theLdlrgene expression, the serum low density lipoprotein level was reducedby 46%, associated with a 30% and 28% decrease in triglyceride and total cholesterol, respectively, compared to uninjectedLdlr−/−mice. Moreover, the TBG directed expression ofLdlrsignificantly decreased the lipid accumulation in liver andreduced plaque burden in aorta (32%). Our results indicated that the hepatocyte-specific expression ofLdlrgene strikinglylowered serum lipid levels and resulted in amelioration of hypercholesterolaemia.

【 授权许可】

Unknown