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(Circulation. 1999;99:105-110.)
© 1999 American Heart Association, Inc.

Basic Science Reports

Somatic Gene Transfer of Human ApoA-I Inhibits Atherosclerosis Progression in Mouse Models

Patrick Benoit, PhD; Florence Emmanuel, PhD; Jean Michel Caillaud, MD; Laurent Bassinet; Graciela Castro, PhD; Pierre Gallix, DVM; Jean Charles Fruchart, PhD; Didier Branellec, PhD; Patrice Denèfle, PhD; Nicolas Duverger, PhD

From Rhône-Poulenc Rorer–Gencell Division, Cardiovascular Department, Centre de recherche de Vitry-Alfortville, Vitry sur Seine, and Institut Pasteur (G.C., J.C.F.), Lille, France.

Correspondence to Nicolas Duverger, Rhône-Poulenc Rorer–Gencell Division, Cardiovascular Department, Centre de recherche de Vitry-Alfortville, 13, Quai Jules Guesde-BP 14, 94403 Vitry sur Seine Cedex, France. E-mail nicolas.duverger{at}rp-rorer.fr

Background—Apolipoprotein (apo) A-I is the major component of HDL, and it displays antiatherogenic properties.

Methods and Results—The human apoA-I gene has been transferred into different mouse models by use of a recombinant adenovirus under the control of an RSV-LTR promoter (AV RSV apoA-I). Administration of AV RSV apoA-I to C57BL/6 mice resulted in moderate expression of human apoA-I for 3 weeks, leading to a transient elevation (40% at day 11 after injection) of HDL cholesterol concentration. In contrast, administration of AV RSV apoA-I to human apoA-I–transgenic mice induced a large increase of human apoA-I and HDL cholesterol concentrations (300% and 360%, respectively, at day 14 after injection) for 10 weeks, indicating that an immune response to the transgene was one major hurdle for long-term duration of expression. Recombinant adenovirus expressing human apolipoprotein A-I (AV RSV apoA-I) was also injected into human apoA-I–transgenic/apoE-deficient mice, which are prone to develop atherosclerosis. Over a 6-week period, overexpression of human apoA-I inhibited fatty streak lesion formation by 56% in comparison with control.

Conclusions—Somatic gene transfer of human apoA-I prevents the development of atherosclerosis in the mouse model.

Key Words: genes • apolipoproteins • atherosclerosis

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