Joke Lievens

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AIMS The ATP-binding cassette transporter A1 (ABCA1) lipidates apolipoprotein (apo) A-I. The hypothesis that hepatocyte-specific ABCA1 overexpression results in high-density lipoprotein (HDL) dysfunction was evaluated by comparing the effects of murine ABCA1 (AdABCA1) and human apo A-I (AdA-I) transfer on lipoprotein profile, HDL function, and progression(More)
BACKGROUND The hallmarks of diabetic cardiomyopathy are cardiac oxidative stress, intramyocardial inflammation, cardiac fibrosis, and cardiac apoptosis. Given the antioxidative, antiinflammatory, and antiapoptotic potential of high-density lipoprotein (HDL), we evaluated the hypothesis that increased HDL via gene transfer (GT) with human apolipoprotein(More)
The hepatotropism and intrahepatic distribution of adenoviral vectors may be species dependent. Hepatocyte transduction was evaluated in three rabbit strains after transfer with E1E3E4-deleted adenoviral vectors containing a hepatocyte specific alpha1-antitrypsin promoter-driven expression cassette (AdAT4). Intravenous administration of 4 x 10(12)(More)
Hepatocytes are a key target for treatment of inborn errors of metabolism, dyslipidemia and coagulation disorders. The development of potent expression cassettes is a critical target to improve the therapeutic index of gene transfer vectors. Here we evaluated 22 hepatocyte-specific expression cassettes containing a human apo A-I transgene following(More)
Apolipoprotein (apo) A-I(Milano) is an apo A-I mutant characterized by a cysteine for arginine substitution at position 173. Apo A-I(Milano) carriers have much less atherosclerosis than expected from their low plasma high-density lipoprotein cholesterol levels, suggesting that this mutant may have superior atheroprotective properties. Here, we compare the(More)
Elimination of Kupffer cells by cytotoxic clodronate liposomes increases transgene expression in the liver after adenoviral transfer. Here, we demonstrate that empty l-alpha-phosphatidylcholine liposomes block uptake of vectors in the reticuloendothelial cells of the liver and increase human apolipoprotein (apo) A-I (approved gene symbol apo A-I) expression(More)
Improvement of the therapeutic index of adenoviral gene transfer requires the development of strategies to abrogate adenoviral capsid-induced inflammation and cytokine production. The effect of monomethoxypolyethylene glycol (MPEG) conjugation to adenoviral vectors and of methylprednisolone (MP) on innate immunity, liver inflammation, and thrombocyte counts(More)
Plasma levels of high-density lipoprotein (HDL) cholesterol and its major apolipoprotein (apo), apo A-I, are inversely correlated with the incidence of ischemic cardiovascular diseases. Reverse cholesterol transport is likely the main mechanism underlying the atheroprotective effects of HDL. Here, we investigated whether increased HDL cholesterol following(More)
Sinusoidal fenestrae may restrict the transport of gene transfer vectors according to their size. Using Vitrobot technology and cryo-electron microscopy, we show that the diameter of human adenoviral serotype 5 vectors is 93 nm with protruding fibers of 30 nm. Thus, a diameter of fenestrae of 150 nm or more is likely to be sufficient for passage of vectors(More)
The liver is a key organ in numerous metabolic pathways, in cholesterol metabolism, and in production of coagulation factors. Therefore, gene transfer to hepatocytes has been extensively pursued. There are numerous biological parameters that may affect the outcome of hepatocyte-directed gene transfer. Species or strain variation of any of these multiple(More)