Adenovirus-mediated transfer of a gene encoding human apolipoprotein A-I into normal mice increases circulating high-density lipoprotein cholesterol

William P. Kopfler, Maureen Willard, Timothy Betz, John E. Willard, Robert D. Gerard, Robert S. Meidell

Research output: Contribution to journalArticle

70 Citations (Scopus)

Abstract

Background: In animal models of atherosclerosis, augmentation of circulating high-density lipoprotein (HDL) cholesterol exerts a protective effect against development of fatty streaks and promotes plaque regression. Methods and Results: To investigate the potential of gene transfer to increase HDL cholesterol, a fusion gene encoding human apolipoprotein A-I (apo A-I) under the control of the human cytomegalovirus (CMV) immediate- early promoter was packaged into a recombinant adenovirus (AdCMV apo A-I). BALB/c mice infected with AdCMV apo A-I by intravenous injection accumulate immunoreactive apo A-I in serum; levels 5 days after infection averaged 168 mg/dL. A 35% increase in HDL cholesterol and a 47% increase in total cholesterol were observed in mice infected with AdCMV apo A-I compared with control viruses. Analysis of size-fractionated lipoproteins revealed that human apo A-I is incorporated into murine HDL particles. Expression of human apo A-I declined to <10% of maximum after 12 days and mRNA encoding apo A-I, prevalent 5 days after infection, was undetectable in the livers of infected mice after 12 days. Conclusions: We conclude that adenovirus-mediated transfer of a gene encoding apo A-I produces transient elevations of circulating HDL cholesterol of a magnitude correlated with important physiological effects. These observations suggest the potential for gene- based therapeutic strategies to reduce cardiovascular risk.

Original languageEnglish (US)
Pages (from-to)1319-1327
Number of pages9
JournalCirculation
Volume90
Issue number3
StatePublished - Sep 1994

Fingerprint

Apolipoprotein A-I
Adenoviridae
HDL Cholesterol
Genes
Lipoprotein(a)
Gene Fusion
HDL Lipoproteins
Infection
Cytomegalovirus
Intravenous Injections
Lipoproteins
human APOA1 protein
Atherosclerosis
Animal Models
Cholesterol
Viruses
Messenger RNA
Liver
Serum

Keywords

  • apolipoproteins
  • atherosclerosis
  • genes
  • lipoproteins
  • viruses

ASJC Scopus subject areas

  • Physiology
  • Cardiology and Cardiovascular Medicine

Cite this

Kopfler, W. P., Willard, M., Betz, T., Willard, J. E., Gerard, R. D., & Meidell, R. S. (1994). Adenovirus-mediated transfer of a gene encoding human apolipoprotein A-I into normal mice increases circulating high-density lipoprotein cholesterol. Circulation, 90(3), 1319-1327.

Adenovirus-mediated transfer of a gene encoding human apolipoprotein A-I into normal mice increases circulating high-density lipoprotein cholesterol. / Kopfler, William P.; Willard, Maureen; Betz, Timothy; Willard, John E.; Gerard, Robert D.; Meidell, Robert S.

In: Circulation, Vol. 90, No. 3, 09.1994, p. 1319-1327.

Research output: Contribution to journalArticle

Kopfler, WP, Willard, M, Betz, T, Willard, JE, Gerard, RD & Meidell, RS 1994, 'Adenovirus-mediated transfer of a gene encoding human apolipoprotein A-I into normal mice increases circulating high-density lipoprotein cholesterol', Circulation, vol. 90, no. 3, pp. 1319-1327.
Kopfler, William P. ; Willard, Maureen ; Betz, Timothy ; Willard, John E. ; Gerard, Robert D. ; Meidell, Robert S. / Adenovirus-mediated transfer of a gene encoding human apolipoprotein A-I into normal mice increases circulating high-density lipoprotein cholesterol. In: Circulation. 1994 ; Vol. 90, No. 3. pp. 1319-1327.
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