Helper-dependent adenoviral vector-mediated long-term expression of human apolipoprotein A-I reduces atherosclerosis in apo E-deficient mice

Lucio Pastore, L. Maria Belalcazar, Kazuhiro Oka, Racel Cela, Brendan Lee, Lawrence Chan, Arthur L. Beaudet

Research output: Contribution to journalArticle

40 Scopus citations

Abstract

Apolipoprotein A-I (APOA-I) is the major protein component of high-density lipoproteins (HDL). It has been shown that over-expression of human APOA-I increases HDL cholesterol and decreases atherosclerosis. We constructed a helper-dependent adenoviral (HD-Ad) vector that contains the entire human APOA-I gene (hgAI). Intravenous delivery of 1×1013 viral particles/kg of this vector was followed by high levels of human APOA-I expression (up to 200 mg/dl) in the absence of detectable hepatic toxicity. We treated apo E-deficient mice with the hgAI vector and fed them either with a high-fat diet or with regular chow. As a control, two groups of mice were treated with PBS. The apo E-deficient mice treated with the hgAI vector showed supraphysiological levels of expression of human APOA-I at week 4 and high levels of HDL cholesterol compared to the control groups. Analysis of aortic atherosclerotic lesions 20 weeks after treatment, showed a significant reduction of lesion size in the treated mice with both diets. In conclusion, liver-directed gene transfer of human APOA-I using a HD-Ad vector resulted in a reduction of the development of atherosclerosis with the absence of significant toxicity.

Original languageEnglish (US)
Pages (from-to)153-160
Number of pages8
JournalGene
Volume327
Issue number2
DOIs
StatePublished - Mar 3 2004

Keywords

  • Apo A-I
  • Helper-dependent adenovirus
  • High-density lipoproteins

ASJC Scopus subject areas

  • Genetics

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