ApoE gene delivery inhibits severe hypercholesterolemia in newborn ApoE-KO mice

Apolipoprotein E, a key regulator in cholesterol-rich lipoprotein metabolism, is considered a strong candidate for treating hypercholesterolemia and cardiovascular disease. Inherited deficiency of this protein results in type III hyperlipoproteinemia in humans. ApoE-knockout mice, which develop spon...

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Bibliographic Details
Published in:Biochemical and biophysical research communications 2007-09, Vol.361 (2), p.543-548
Main Authors: Signori, Emanuela, Rinaldi, Monica, Fioretti, Daniela, Iurescia, Sandra, Seripa, Davide, Perrone, Giuseppe, Norata, Giuseppe Danilo, Catapano, Alberico Luigi, Fazio, Vito Michele
Format: Article
Language:English
Subjects:
Animals
Animals, Newborn
Antibodies
ApolipoproteinE
Apolipoproteins E - administration & dosage
Apolipoproteins E - deficiency
Apolipoproteins E - genetics
Atherosclerosis - pathology
Cholesterol - blood
DNA, Complementary - administration & dosage
Female
Genetic Therapy
Genetic Vectors
Hypercholesterolemia
Hypercholesterolemia - genetics
Hypercholesterolemia - prevention & control
Immunity
Injections, Intramuscular
Intramuscular gene transfer
Male
Mice
Mice, Knockout
Neonatal gene therapy
Plasmid vector
Plasmids - metabolism
Time Factors
Transfection
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Summary:Apolipoprotein E, a key regulator in cholesterol-rich lipoprotein metabolism, is considered a strong candidate for treating hypercholesterolemia and cardiovascular disease. Inherited deficiency of this protein results in type III hyperlipoproteinemia in humans. ApoE-knockout mice, which develop spontaneous hypercholesterolemia, are an excellent model of human atherosclerosis. Here we investigated the therapeutic effects of a plasmid vector encoding human APOE3 sequence intramuscularly injected in hypercholesterolemic newborn mice at the ages of 5 and 14 days. We further explored the possibility of inducing tolerance in newborns when injected early. Our data show that direct i.m. naked DNA injection reduces severe hypercholesterolemia in newborn mice. Moreover, when naked DNA is administrated early, no immune response is generated against the human APOE, allowing repeated administrations. Neonatal therapies are important for the treatment of many genetic childhood diseases where early administration is required to prevent developmental damage. We propose the use of direct i.m. naked gene transfer in newborns to prevent long-term damages arising from hypercholesterolemic conditions.
ISSN:0006-291X
1090-2104
DOI:10.1016/j.bbrc.2007.07.046