In vivo imaging shows abnormal function of vascular endothelial growth factor-induced vasculature

Autor: ZACCHIGNA, S, TASCIOTTI, E, KUSMIC, C, ARSIC, N, SORACE, O, MARINI, C, MARZULLO, P, PARDINI, S, PETRONI, D, PATTARINI, L, MOIMAS, SILVIA, GIACCA, MAURO, M, SAMBUCETI
Přispěvatelé: Zacchigna, S, Tasciotti, E, Kusmic, C, Arsic, N, Sorace, O, Marini, C, Marzullo, P, Pardini, S, Petroni, D, Pattarini, L, Moimas, Silvia, Giacca, Mauro, M, Sambuceti
Jazyk: angličtina
Rok vydání: 2007
Předmět:
Male
Vascular Endothelial Growth Factor A
Pathology
Angiogenesis
Wistar
Gene Expression
Vascular permeability
chemistry.chemical_compound
Models
Tomography
medicine.diagnostic_test
Neovascularization
Pathologic

Skeletal
Dependovirus
Dependoviru
Vascular endothelial growth factor
medicine.anatomical_structure
Models
Animal

Molecular Medicine
Radiopharmaceutical
Muscle
Technetium Tc 99m Pentetate
Genetic Vector
Perfusion
Preclinical imaging
medicine.medical_specialty
Endothelium
Genetic Vectors
Biology
Transfection
Capillary Permeability
Vascular
medicine
Angiopoietin-1
Genetics
Animals
Rats
Wistar

Muscle
Skeletal

Molecular Biology
Neovascularization
Tomography
Emission-Computed
Single-Photon

Pathologic
Animal
Skeletal muscle
Rats
chemistry
Positron-Emission Tomography
Rat
Endothelium
Vascular

Radiopharmaceuticals
Emission-Computed
Emission computed tomography
Single-Photon
Popis: Although the angiogenic effect of vascular endothelial growth factor (VEGF) is widely recognized, a central question concerns whether the vessels formed on its overexpression effectively increase tissue perfusion in vivo. To explore this issue, here we exploit AAV vectors to obtain the prolonged expression of VEGF and angiopoietin- 1 (Ang1) in rat skeletal muscle. Over a period of 6 months, muscle blood flow (MBF) and vascular permeability were measured by positron emission tomography and single-photon emission computed tomography, respectively. All measurements were performed under resting conditions and after electrically induced muscle exercise. Despite the potent angiogenic effect of VEGF, documented by vessel counting and intravascular volume assessment, the expression of this factor did not improve resting MBF, and it even decreased perfusion after exercise. This deleterious effect was related to the formation of leaky vascular lacunae, which accounted for the occurrence of arteriovenous shunts that excluded the downstream microcirculation. These effects were significantly counteracted by the coinjection of VEGF and Ang1, which determined a marked increase in resting MBF and, most notably, a significant improvement after exercise that persisted over time. Taken together, these results challenge the effectiveness of VEGF as a sole factor to induce angiogenesis and suggest the use of factor combinations to achieve competent vessel formation.
Databáze: OpenAIRE
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