首页> 中文期刊> 《生物医学研究杂志(英文版)》 >Apolipoprotein A-V gene therapy for disease prevention / treatment: a critical analysis

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

         

摘要

Apolipoprotein(apo) A-V is a novel member of the class of exchangeable apo's involved in triacylglycerol(TG)homeostasis.Whereas 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 droplets.Loss of apo A-V function is positively correlated with elevated plasma TG and increased risk of cardiovascular disease.Single nucleotide polymorphisms(SNP) in the APOA5 locus can affect transcription efficiency or introduce deleterious amino acid substitutions.Likewise,rare mutations in APOA5 that compromise functionality are associated with increased plasma TG and premature myocardial infarction.Genetically engineered mouse models and human population studies suggest that,in certain instances,supplementation with wild type(WT) apoA-V may have therapeutic benefit.It 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 clearance.On the other hand,subjects with hypertriglyceridemia of independent origin(unrelated to apoA-V function) may not respond to apoA-V augmentation in this manner.Improvement 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 strategy.Candidates 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.

著录项

  • 来源
    《生物医学研究杂志(英文版)》 |2016年第2期|88-93|共6页
  • 作者单位

    Center for Prevention of Obesity, Diabetes and Cardiovascular Disease, Children's Hospital Oakland Research Institute,Oakland, CA 94609, USA;

    Center for Prevention of Obesity, Diabetes and Cardiovascular Disease, Children's Hospital Oakland Research Institute,Oakland, CA 94609, USA;

    Center for Prevention of Obesity, Diabetes and Cardiovascular Disease, Children's Hospital Oakland Research Institute,Oakland, CA 94609, USA;

  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类 脂肪代谢障碍;
  • 关键词

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