Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Post, H; Kajstura, J; Lei, B; Sessa, WC; Byrne, B; Anversa, P; Hintze, TH; Recchia, FA.
Adeno-associated virus mediated gene delivery into coronary microvessels of chronically instrumented dogs.
J Appl Physiol. 2003; 95(4):1688-1694
Doi: 10.1152/japplphysiol.00896.2002
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- Führende Autor*innen der Med Uni Graz
- Post Heiner
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- Abstract:
- 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.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
- Coronary Vessels - metabolism
- Dependovirus - metabolism
- Dogs - metabolism
- Endothelium, Vascular - cytology
- Gene Transfer Techniques - cytology
- Genetic Vectors - cytology
- Green Fluorescent Proteins - cytology
- Hemodynamics - cytology
- Immunohistochemistry - cytology
- Indicators and Reagents - pharmacokinetics
- Leukocyte Count - pharmacokinetics
- Luminescent Proteins - genetics
- Microscopy, Confocal - genetics
- Myocytes, Smooth Muscle - metabolism
- Neutrophils - cytology
- Tissue Distribution - cytology
- Transduction, Genetic - cytology
- Find related publications in this database (Keywords)
- white cells
- hemodynamics
- green fluorescent protein
- von Willebrand factor