Overexpression of ABCG1 protein attenuates arteriosclerosis and endothelial dysfunction in atherosclerotic rabbits
Abstract
Overview
The ABCG1 protein is centrally involved in
reverse cholesterol transport from the vessel
wall. Investigation of the effects of ABCG1
overexpression or knockdown in vivo has produced
controversial results and strongly
depended on the gene intervention model in
which it was studied. Therefore, we investigated
the effect of local overexpression of
human ABCG1 in a novel model of vessel walldirected
adenoviral gene transfer in atherosclerotic
rabbits. We conducted local, vascularspecific
gene transfer by adenoviral delivery of
human ABCG1 (Ad-ABCG1-GFP) in cholesterol-
fed atherosclerotic rabbits in vivo.
Endothelial overexpression of ABCG1 markedly
reduced atheroprogression (plaque size)
and almost blunted vascular inflammation, as
shown by markedly reduced macrophage and
smooth muscle cell invasion into the vascular
wall. Also endothelial function, as determined
by vascular ultrasound in vivo, was improved
in rabbits after gene transfer with Ad-ABCG1-
GFP. Therefore, both earlier and later stages of
atherosclerosis were improved in this model
of somatic gene transfer into the vessel wall.
In contrast to results in transgenic mice, overexpression
of ABCG1 by somatic gene transfer
to the atherosclerotic vessel wall results in a
significant improvement of plaque morphology
and composition, and of vascular function
in vivo.
Keywords
Adenoviral vector, gene transfer, ABCG1, atherosclerosis.
Article Information
Correspondence
Martin Ungerer; Corimmun GmbH; Fraunhofer Str. 17; D-82152 Martinsried, Germany. Tel. +49.89.85652010 – Fax: +49.89.85652020 E-email: ungerer@corimmun.com
Received
2011-12-07T00:00:00
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