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PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
4
pubmed:dateCreated
2003-9-12
pubmed:abstractText
The objective of this study was to assess the potential of adeno-associated virus (AAV)-mediated gene delivery into coronary microvessels in vivo in a large animal. Ten mongrel dogs were chronically instrumented and allowed to recover for 10 days. Dogs were reanesthetized, and the aorta was constricted by a hydraulic occluder, whereby left ventricular (LV) pressure increased by 30% and left circumflex coronary artery blood flow by 50%. Recombinant AAV (serotype 2, CMV enhancer/chicken beta-actin promoter) encoding for green fluorescent protein (GFP) was injected as a bolus into the left atrium during aortic constriction at total titers of 1010 or 1012 infectious units. Dogs were followed for 2 (n = 4)or4wk(n = 6). Hemodynamics or body weight did not change. In LV tissue slices, a fluorescein-labeled antibody to GFP stained endothelial and smooth muscle cells but was absent in myocytes. To quantify transduction, slices were then stained with antibodies against alpha-smooth muscle actin or von Willebrand factor. Approximately 4% of arterioles and 2% of microvessels stained positive for anti-GFP independent from viral titer or duration. By regression analyses, the percent of vessels transfected was proportional to the increase in LV systolic pressure during occlusion. AAV is a potential vector for gene transfer into the coronary microcirculation in large animals, including perhaps humans.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
8750-7587
pubmed:author
pubmed:issnType
Print
pubmed:volume
95
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1688-94
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed-meshheading:12844500-Animals, pubmed-meshheading:12844500-Coronary Vessels, pubmed-meshheading:12844500-Dependovirus, pubmed-meshheading:12844500-Dogs, pubmed-meshheading:12844500-Endothelium, Vascular, pubmed-meshheading:12844500-Gene Transfer Techniques, pubmed-meshheading:12844500-Genetic Vectors, pubmed-meshheading:12844500-Green Fluorescent Proteins, pubmed-meshheading:12844500-Hemodynamics, pubmed-meshheading:12844500-Immunohistochemistry, pubmed-meshheading:12844500-Indicators and Reagents, pubmed-meshheading:12844500-Leukocyte Count, pubmed-meshheading:12844500-Luminescent Proteins, pubmed-meshheading:12844500-Microscopy, Confocal, pubmed-meshheading:12844500-Myocytes, Smooth Muscle, pubmed-meshheading:12844500-Neutrophils, pubmed-meshheading:12844500-Tissue Distribution, pubmed-meshheading:12844500-Transduction, Genetic
pubmed:year
2003
pubmed:articleTitle
Adeno-associated virus mediated gene delivery into coronary microvessels of chronically instrumented dogs.
pubmed:affiliation
Dept. of Physiology, Basic Sciences Bldg., Rm. 636, New York Medical College, Valhalla, NY 10595, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't