Vasomotor dysfunction early after exposure of normal rabbit arteries to an adenoviral vector

Human Gene Therapy
A LafontD Escande

Abstract

We aimed to investigate whether infection of normal rabbit arteries with a recombinant adenovirus vector would result per se in alterations in contractile and endothelial functions. In one group of rabbits, right or left femoral and ear artery segments were injected in vivo with a replication-deficient adenoviral vector expressing a beta-galactosidase (beta-Gal) reporter gene (4 x 10(10) pfu/ml) to demonstrate efficient gene transfer. Contralateral arteries were injected with the same concentration of a recombinant adenoviral vector carrying no transgene (Ad.MLPnull). In another group of animals, Ad.MLPnull was injected into the lumen of femoral and ear artery segments. The contralateral arteries were used as controls with the injection of vehicle alone. Histochemical assessment of gene transfer using beta-Gal activity (group 1) or in vitro contractility and endothelial function (group 2) was performed 3 days after adenoviral infection. Gene transfer was efficient and reproducible in the endothelium and was associated with the presence of inflammatory cells in the media. In Ad.MLPnull-injected arteries, in vitro contractile response of femoral artery rings to either KCl 60 mM or phenylephrine (10 microM) was reduced to 10.5 +/-...Continue Reading

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