Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes.
Identifieur interne : 009497 ( Main/Exploration ); précédent : 009496; suivant : 009498Adenoviral VEGF-C overexpression induces blood vessel enlargement, tortuosity, and leakiness but no sprouting angiogenesis in the skin or mucous membranes.
Auteurs : Anne Saaristo [Finlande] ; Tanja Veikkola ; Berndt Enholm ; Maija Hytönen ; Johanna Arola ; Katri Pajusola ; Païvi Turunen ; Michael Jeltsch ; Marika J. Karkkainen ; Dontscho Kerjaschki ; Hansruedi Bueler ; Seppo Yl Herttuala ; Kari Alitalo [Finlande]Source :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ 1530-6860 ] ; 2002.
Descripteurs français
- KwdFr :
- Adenoviridae (génétique), Angiopoïétine-1, Animaux, Dependovirus (génétique), Facteur de croissance endothéliale vasculaire de type A, Facteur de croissance endothéliale vasculaire de type C, Facteurs de croissance endothéliale (génétique), Facteurs de croissance endothéliale (métabolisme), Facteurs de croissance endothéliale vasculaire, Glycoprotéines membranaires (pharmacologie), Lignée cellulaire, Lymphokines (génétique), Muqueuse nasale (), Néovascularisation physiologique, Peau (), Peau (métabolisme), Perméabilité capillaire (), Récepteur facteur croissance (métabolisme), Récepteurs aux facteurs de croissance endothéliale vasculaire, Récepteurs à activité tyrosine kinase (métabolisme), Souris, Souris nude, Système lymphatique (croissance et développement), Transfection, Vaisseaux sanguins (anatomie et histologie), Vaisseaux sanguins (métabolisme), Vecteurs génétiques.
- MESH :
- anatomie et histologie : Vaisseaux sanguins.
- croissance et développement : Système lymphatique.
- génétique : Adenoviridae, Dependovirus, Facteurs de croissance endothéliale, Lymphokines.
- métabolisme : Facteurs de croissance endothéliale, Peau, Récepteur facteur croissance, Récepteurs à activité tyrosine kinase, Vaisseaux sanguins.
- pharmacologie : Glycoprotéines membranaires.
- Angiopoïétine-1, Animaux, Facteur de croissance endothéliale vasculaire de type A, Facteur de croissance endothéliale vasculaire de type C, Facteurs de croissance endothéliale vasculaire, Lignée cellulaire, Muqueuse nasale, Néovascularisation physiologique, Peau, Perméabilité capillaire, Récepteurs aux facteurs de croissance endothéliale vasculaire, Souris, Souris nude, Transfection, Vecteurs génétiques.
English descriptors
- KwdEn :
- Adenoviridae (genetics), Angiopoietin-1, Animals, Blood Vessels (anatomy & histology), Blood Vessels (metabolism), Capillary Permeability (drug effects), Cell Line, Dependovirus (genetics), Endothelial Growth Factors (genetics), Endothelial Growth Factors (metabolism), Genetic Vectors, Lymphatic System (growth & development), Lymphokines (genetics), Membrane Glycoproteins (pharmacology), Mice, Mice, Nude, Nasal Mucosa (blood supply), Neovascularization, Physiologic, Receptor Protein-Tyrosine Kinases (metabolism), Receptors, Growth Factor (metabolism), Receptors, Vascular Endothelial Growth Factor, Skin (blood supply), Skin (metabolism), Transfection, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factors.
- MESH :
- chemical , genetics : Endothelial Growth Factors, Lymphokines.
- chemical , metabolism : Endothelial Growth Factors, Receptor Protein-Tyrosine Kinases, Receptors, Growth Factor.
- chemical , pharmacology : Membrane Glycoproteins.
- chemical : Angiopoietin-1, Receptors, Vascular Endothelial Growth Factor, Vascular Endothelial Growth Factor A, Vascular Endothelial Growth Factor C, Vascular Endothelial Growth Factors.
- anatomy & histology : Blood Vessels.
- blood supply : Nasal Mucosa, Skin.
- drug effects : Capillary Permeability.
- genetics : Adenoviridae, Dependovirus.
- growth & development : Lymphatic System.
- metabolism : Blood Vessels, Skin.
- Animals, Cell Line, Genetic Vectors, Mice, Mice, Nude, Neovascularization, Physiologic, Transfection.
Abstract
Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. The VEGF-C/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and heterozygous inactivating missense mutations of the VEGFR-3 gene are associated with hereditary lymphedema. However, VEGF-C can have potent effects on blood vessels because its receptor VEGFR-3 is expressed in certain blood vessels and because the fully processed form of VEGF-C also binds to the VEGFR-2 of blood vessels. To characterize the in vivo effects of VEGF-C on blood and lymphatic vessels, we have overexpressed VEGF-C via adenovirus- and adeno-associated virus-mediated transfection in the skin and respiratory tract of athymic nude mice. This resulted in dose-dependent enlargement and tortuosity of veins, which, along with the collecting lymphatic vessels were found to express VEGFR-2. Expression of angiopoietin 1 blocked the increased leakiness of the blood vessels induced by VEGF-C whereas vessel enlargement and lymphangiogenesis were not affected. However, angiogenic sprouting of new blood vessels was not observed in response to AdVEGF-C or AAV-VEGF-C. These results show that virally produced VEGF-C induces blood vessel changes, including vascular leak, but its angiogenic potency is much reduced compared with VEGF in normal skin.
DOI: 10.1096/fj.01-1042com
PubMed: 12087065
Affiliations:
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(metabolism)</term><term>Receptors, Vascular Endothelial Growth Factor</term><term>Skin (blood supply)</term><term>Skin (metabolism)</term><term>Transfection</term><term>Vascular Endothelial Growth Factor A</term><term>Vascular Endothelial Growth Factor C</term><term>Vascular Endothelial Growth Factors</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adenoviridae (génétique)</term><term>Angiopoïétine-1</term><term>Animaux</term><term>Dependovirus (génétique)</term><term>Facteur de croissance endothéliale vasculaire de type A</term><term>Facteur de croissance endothéliale vasculaire de type C</term><term>Facteurs de croissance endothéliale (génétique)</term><term>Facteurs de croissance endothéliale (métabolisme)</term><term>Facteurs de croissance endothéliale vasculaire</term><term>Glycoprotéines membranaires (pharmacologie)</term><term>Lignée cellulaire</term><term>Lymphokines (génétique)</term><term>Muqueuse nasale ()</term><term>Néovascularisation physiologique</term><term>Peau ()</term><term>Peau (métabolisme)</term><term>Perméabilité capillaire ()</term><term>Récepteur facteur croissance (métabolisme)</term><term>Récepteurs aux facteurs de croissance endothéliale vasculaire</term><term>Récepteurs à activité tyrosine kinase (métabolisme)</term><term>Souris</term><term>Souris nude</term><term>Système lymphatique (croissance et développement)</term><term>Transfection</term><term>Vaisseaux sanguins (anatomie et histologie)</term><term>Vaisseaux sanguins (métabolisme)</term><term>Vecteurs génétiques</term></keywords><keywords scheme="MESH" type="chemical" qualifier="genetics" xml:lang="en"><term>Endothelial Growth Factors</term><term>Lymphokines</term></keywords><keywords scheme="MESH" type="chemical" qualifier="metabolism" xml:lang="en"><term>Endothelial Growth Factors</term><term>Receptor Protein-Tyrosine Kinases</term><term>Receptors, Growth Factor</term></keywords><keywords scheme="MESH" type="chemical" qualifier="pharmacology" xml:lang="en"><term>Membrane Glycoproteins</term></keywords><keywords scheme="MESH" type="chemical" xml:lang="en"><term>Angiopoietin-1</term><term>Receptors, Vascular Endothelial Growth Factor</term><term>Vascular Endothelial Growth Factor A</term><term>Vascular Endothelial Growth Factor C</term><term>Vascular Endothelial Growth Factors</term></keywords><keywords scheme="MESH" qualifier="anatomie et histologie" xml:lang="fr"><term>Vaisseaux sanguins</term></keywords><keywords scheme="MESH" qualifier="anatomy & histology" xml:lang="en"><term>Blood Vessels</term></keywords><keywords scheme="MESH" qualifier="blood supply" xml:lang="en"><term>Nasal Mucosa</term><term>Skin</term></keywords><keywords scheme="MESH" qualifier="croissance et développement" xml:lang="fr"><term>Système lymphatique</term></keywords><keywords scheme="MESH" qualifier="drug effects" xml:lang="en"><term>Capillary Permeability</term></keywords><keywords scheme="MESH" qualifier="genetics" xml:lang="en"><term>Adenoviridae</term><term>Dependovirus</term></keywords><keywords scheme="MESH" qualifier="growth & development" xml:lang="en"><term>Lymphatic System</term></keywords><keywords scheme="MESH" qualifier="génétique" xml:lang="fr"><term>Adenoviridae</term><term>Dependovirus</term><term>Facteurs de croissance endothéliale</term><term>Lymphokines</term></keywords><keywords scheme="MESH" qualifier="metabolism" xml:lang="en"><term>Blood Vessels</term><term>Skin</term></keywords><keywords scheme="MESH" qualifier="métabolisme" xml:lang="fr"><term>Facteurs de croissance endothéliale</term><term>Peau</term><term>Récepteur facteur croissance</term><term>Récepteurs à activité tyrosine kinase</term><term>Vaisseaux sanguins</term></keywords><keywords scheme="MESH" qualifier="pharmacologie" xml:lang="fr"><term>Glycoprotéines membranaires</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Cell Line</term><term>Genetic Vectors</term><term>Mice</term><term>Mice, Nude</term><term>Neovascularization, Physiologic</term><term>Transfection</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Angiopoïétine-1</term><term>Animaux</term><term>Facteur de croissance endothéliale vasculaire de type A</term><term>Facteur de croissance endothéliale vasculaire de type C</term><term>Facteurs de croissance endothéliale vasculaire</term><term>Lignée cellulaire</term><term>Muqueuse nasale</term><term>Néovascularisation physiologique</term><term>Peau</term><term>Perméabilité capillaire</term><term>Récepteurs aux facteurs de croissance endothéliale vasculaire</term><term>Souris</term><term>Souris nude</term><term>Transfection</term><term>Vecteurs génétiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Vascular endothelial growth factors (VEGFs) and their receptors (VEGFRs) are important regulators of blood and lymphatic vessel growth and vascular permeability. The VEGF-C/VEGFR-3 signaling pathway is crucial for lymphangiogenesis, and heterozygous inactivating missense mutations of the VEGFR-3 gene are associated with hereditary lymphedema. However, VEGF-C can have potent effects on blood vessels because its receptor VEGFR-3 is expressed in certain blood vessels and because the fully processed form of VEGF-C also binds to the VEGFR-2 of blood vessels. To characterize the in vivo effects of VEGF-C on blood and lymphatic vessels, we have overexpressed VEGF-C via adenovirus- and adeno-associated virus-mediated transfection in the skin and respiratory tract of athymic nude mice. This resulted in dose-dependent enlargement and tortuosity of veins, which, along with the collecting lymphatic vessels were found to express VEGFR-2. Expression of angiopoietin 1 blocked the increased leakiness of the blood vessels induced by VEGF-C whereas vessel enlargement and lymphangiogenesis were not affected. However, angiogenic sprouting of new blood vessels was not observed in response to AdVEGF-C or AAV-VEGF-C. These results show that virally produced VEGF-C induces blood vessel changes, including vascular leak, but its angiogenic potency is much reduced compared with VEGF in normal skin.</div></front></TEI><affiliations><list><country><li>Finlande</li></country><region><li>Uusimaa</li></region><settlement><li>Helsinki</li></settlement><orgName><li>Université d'Helsinki</li></orgName></list><tree><noCountry><name sortKey="Arola, Johanna" sort="Arola, Johanna" uniqKey="Arola J" first="Johanna" last="Arola">Johanna Arola</name><name sortKey="Bueler, Hansruedi" sort="Bueler, Hansruedi" uniqKey="Bueler H" first="Hansruedi" last="Bueler">Hansruedi Bueler</name><name sortKey="Enholm, Berndt" sort="Enholm, Berndt" uniqKey="Enholm B" first="Berndt" last="Enholm">Berndt Enholm</name><name sortKey="Hytonen, Maija" sort="Hytonen, Maija" uniqKey="Hytonen M" first="Maija" last="Hytönen">Maija Hytönen</name><name sortKey="Jeltsch, Michael" sort="Jeltsch, Michael" uniqKey="Jeltsch M" first="Michael" last="Jeltsch">Michael Jeltsch</name><name sortKey="Karkkainen, Marika J" sort="Karkkainen, Marika J" uniqKey="Karkkainen M" first="Marika J" last="Karkkainen">Marika J. Karkkainen</name><name sortKey="Kerjaschki, Dontscho" sort="Kerjaschki, Dontscho" uniqKey="Kerjaschki D" first="Dontscho" last="Kerjaschki">Dontscho Kerjaschki</name><name sortKey="Pajusola, Katri" sort="Pajusola, Katri" uniqKey="Pajusola K" first="Katri" last="Pajusola">Katri Pajusola</name><name sortKey="Turunen, Paivi" sort="Turunen, Paivi" uniqKey="Turunen P" first="Païvi" last="Turunen">Païvi Turunen</name><name sortKey="Veikkola, Tanja" sort="Veikkola, Tanja" uniqKey="Veikkola T" first="Tanja" last="Veikkola">Tanja Veikkola</name><name sortKey="Yl Herttuala, Seppo" sort="Yl Herttuala, Seppo" uniqKey="Yl Herttuala S" first="Seppo" last="Yl Herttuala">Seppo Yl Herttuala</name></noCountry><country name="Finlande"><noRegion><name sortKey="Saaristo, Anne" sort="Saaristo, Anne" uniqKey="Saaristo A" first="Anne" last="Saaristo">Anne Saaristo</name></noRegion><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name></country></tree></affiliations></record>Pour manipuler ce document sous Unix (Dilib)
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