Apolipoprotein A-V gene therapy for disease prevention/treatment:a critical analysis

作     者：Trudy M.Forte Vineeta Sharma Robert O.Ryan 

作者机构：Center for Prevention of ObesityDiabetes and Cardiovascular DiseaseChildren's Hospital Oakland Research Institute 

出 版 物：《The Journal of Biomedical Research》 (生物医学研究杂志（英文版）)

年 卷 期：2016年第30卷第2期

页      面：88-93页

核心收录：

学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学] 

基　　金：Supported by a grant from NIH(R37-HL64159) an AHA Postdoctoral Fellowship Award(VS) 

主　　题：apolipoprotein A V adeno associated virus triacylglycerol lipoprotein lipase atherosclerosis single nucleotide polymorphism gene therapy 

摘      要：Apolipoprotein（apo） A-V is a novel member of the class of exchangeable apo＇s involved in triacylglycerol（TG）*** a portion of hepatic-derived apoA-V is secreted into plasma and functions to facilitate lipoprotein Iipase-mediated TG hydrolysis,another portion is recovered intracellularly,in association with cytosolic lipid *** of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular *** nucleotide polymorphisms（SNP） in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid ***,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial *** engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type（WT） apoA-V may have therapeutic *** is hypothesized that individuals that manifest elevated plasma TG owing to deleterious APOA5 SNPs or rare mutations would respond to WT apoA-V supplementation with improved plasma TG *** the other hand,subjects with hypertriglyceridemia of independent origin（unrelated to apoA-V function） may not respond to apoA-V augmentation in this *** in the ability to identify individuals predicted to benefit,advances in gene transfer technology and the strong connection between HTG and heart disease,point to apoA-V supplementation as a viable disease prevention / therapeutic *** would include individuals that manifest chronic TG elevation,have low plasma apoA-V due to an APOA5 mutation/polymorphism and not have deleterious mutations/polymorphisms in other genes known to influence plasma TG levels.