Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0001486 (Adenovirus)
 3,125 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Adenovirus-mediated gene transfer to blood vessels is relatively inefficient because binding of adenovirus to vessels is limited. The authors have reported that incorporation of cationic polymer and lipids with adenovirus augments gene transfer to blood vessels ex vivo. In this study, the authors determined whether complexes of adenovirus and cations improve efficiency of gene transfer in vivo. Poly-L-lysine, lipofectamine, or lipofectin was complexed with adenovirus encoding beta-galactosidase. Optimum ratios of the cations per adenovirus were determined by gene transfer to fibroblasts. After injection of the adenovirus into the cisterna magna of anesthetized rabbits, transgene activity was greater in the adventitia of intracranial arteries and meninges after injection of the complexes than adenovirus alone. Thirty minutes after application of adenovirus with the cations, binding of adenovirus to fibroblast cells in vitro or the basilar artery in vivo (by Southern blot analysis) was augmented, which suggests that enhanced binding of virus contributes to augmentation of transgene expression. Thus, cationic polymer and lipids improve transgene expression in intracranial arteries, primarily in the adventitia, after adenovirus-mediated gene transfer in vivo. This strategy may be applicable to studies of gene transfer and eventually for gene therapy.
J Cereb Blood Flow Metab 2001 Sep
PMID:Cationic polymer and lipids augment adenovirus-mediated gene transfer to cerebral arteries in vivo. 1152 17

Vascular endothelial growth factor (VEGF) induces increased vessel permeability and formation of abnormal vessels. To investigate cerebral blood flow (CBF) during local overexpression of VEGF recombinant adenoviruses carrying the human VEGF165 complementary DNA (2.3 to 23. 108 pfu/mL) were injected stereotactically into the caudate nucleus of anesthetized rats. Saline and adenoviruses carrying the beta-galactosidase gene served as controls. Eleven days later (1) size and density of vessels were assessed in hematoxylin-eosin-stained sections, (2) vascular permeability was measured by intravenous Evans blue injections, and (3) local CBF (lCBF) was quantified using the iodo-[14C]antipyrine technique. Dose-dependent increases were found in (1) vessel density and size (only vessels >43 microm could be quantified morphologically), (2) Evans blue extravasation and brain edema formation, and (3) lCBF (up to eightfold). At medium doses, hyperemic areas and smaller areas of decreased lCBF were found. In low flow areas, vascular cross-sectional areas were increased 223-fold and vessel density up to 10-fold. In high flow areas, these parameters were increased 32-fold and up to 15-fold, respectively. Adenovirus mediated VEGF overexpression results in (1) increased vessel size and density, (2) areas of increased and of decreased flow, and (3) more and smaller vessels in high flow than in low flow areas. These results indicate a diverging flow pattern of newly formed vessels.
J Cereb Blood Flow Metab 2003 Apr
PMID:Heterologous expression of human VEGF165 in rat brain: dose-dependent, heterogeneous effects on CBF in relation to vascular density and cross-sectional area. 1267 19