Vascular endothelial growth factor-C gene therapy restores lymphatic flow across incision wounds.
Identifieur interne : 008683 ( Main/Exploration ); précédent : 008682; suivant : 008684Vascular endothelial growth factor-C gene therapy restores lymphatic flow across incision wounds.
Auteurs : Anne Saaristo [Finlande] ; Tuomas Tammela ; Jari Timonen ; Seppo Yla-Herttuala ; Erkki Tukiainen ; Sirpa Asko-Seljavaara ; Kari Alitalo [Finlande]Source :
- FASEB journal : official publication of the Federation of American Societies for Experimental Biology [ 1530-6860 ] ; 2004.
Descripteurs français
- KwdFr :
- Adenoviridae (génétique), Animaux, Complications postopératoires (), Facteur de croissance endothéliale vasculaire de type C (génétique), Lymphe (physiologie), Thérapie génétique, Vaisseaux lymphatiques (), Vaisseaux lymphatiques (physiologie), Vaisseaux lymphatiques (traumatismes), Vecteurs génétiques.
- MESH :
- génétique : Adenoviridae, Facteur de croissance endothéliale vasculaire de type C.
- physiologie : Lymphe, Vaisseaux lymphatiques.
- traumatismes : Vaisseaux lymphatiques.
- Animaux, Complications postopératoires, Thérapie génétique, Vaisseaux lymphatiques, Vecteurs génétiques.
English descriptors
- KwdEn :
- MESH :
- chemical , genetics : Vascular Endothelial Growth Factor C.
- genetics : Adenoviridae.
- injuries : Lymphatic Vessels.
- physiology : Lymph, Lymphatic Vessels.
- surgery : Lymphatic Vessels.
- therapy : Postoperative Complications.
- Animals, Genetic Therapy, Genetic Vectors.
Abstract
Edema and insufficient blood perfusion are common problems in reconstructive surgery. The blood vasculature is reconstructed in microvascular flaps, whereas lymphatic vessel function is lost after surgical incision. Here, we demonstrate that vascular endothelial growth factor C (VEGF-C) gene transfer can be used to reconstruct a lymphatic vessel network severed by incision of skin flaps. We used adenoviral VEGF-C gene transfer at the edges of epigastric skin flaps in mice. Our results show that VEGF-C gene expression results in the formation of anastomoses between the lymphatic vessels of the skin flap and the surrounding lymphatic vasculature. Some spontaneous lymphangiogenesis also took place in the control mice, but the lymphatic vessels generated remained nonfunctional even 2 months postoperatively. In contrast, the VEGF-C treated mice demonstrated persistent lymphatic vessel function during the 2 month follow-up despite the transient nature of the adenoviral VEGF-C gene expression. The restoration of lymphatic function by VEGF-C in skin flaps provides new tools to promote vascular perfusion and to reduce tissue edema in skin and muscle flaps. These results have important implications for the prevention and treatment of surgically induced secondary lymphedema.
DOI: 10.1096/fj.04-1592fje
PubMed: 15361472
Affiliations:
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first="Tuomas" last="Tammela">Tuomas Tammela</name></author><author><name sortKey="Timonen, Jari" sort="Timonen, Jari" uniqKey="Timonen J" first="Jari" last="Timonen">Jari Timonen</name></author><author><name sortKey="Yla Herttuala, Seppo" sort="Yla Herttuala, Seppo" uniqKey="Yla Herttuala S" first="Seppo" last="Yla-Herttuala">Seppo Yla-Herttuala</name></author><author><name sortKey="Tukiainen, Erkki" sort="Tukiainen, Erkki" uniqKey="Tukiainen E" first="Erkki" last="Tukiainen">Erkki Tukiainen</name></author><author><name sortKey="Asko Seljavaara, Sirpa" sort="Asko Seljavaara, Sirpa" uniqKey="Asko Seljavaara S" first="Sirpa" last="Asko-Seljavaara">Sirpa Asko-Seljavaara</name></author><author><name sortKey="Alitalo, Kari" sort="Alitalo, Kari" uniqKey="Alitalo K" first="Kari" last="Alitalo">Kari Alitalo</name><affiliation><country>Finlande</country><placeName><settlement type="city">Helsinki</settlement><region type="région" nuts="2">Uusimaa</region></placeName><orgName type="university">Université d'Helsinki</orgName></affiliation></author></analytic><series><title level="j">FASEB journal : official publication of the Federation of American Societies for Experimental Biology</title><idno type="eISSN">1530-6860</idno><imprint><date when="2004" type="published">2004</date></imprint></series></biblStruct></sourceDesc></fileDesc><profileDesc><textClass><keywords scheme="KwdEn" xml:lang="en"><term>Adenoviridae (genetics)</term><term>Animals</term><term>Genetic Therapy</term><term>Genetic Vectors</term><term>Lymph (physiology)</term><term>Lymphatic Vessels (injuries)</term><term>Lymphatic Vessels (physiology)</term><term>Lymphatic Vessels (surgery)</term><term>Postoperative Complications (therapy)</term><term>Vascular Endothelial Growth Factor C (genetics)</term></keywords><keywords scheme="KwdFr" xml:lang="fr"><term>Adenoviridae (génétique)</term><term>Animaux</term><term>Complications postopératoires ()</term><term>Facteur de croissance endothéliale 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Vessels</term></keywords><keywords scheme="MESH" qualifier="surgery" xml:lang="en"><term>Lymphatic Vessels</term></keywords><keywords scheme="MESH" qualifier="therapy" xml:lang="en"><term>Postoperative Complications</term></keywords><keywords scheme="MESH" qualifier="traumatismes" xml:lang="fr"><term>Vaisseaux lymphatiques</term></keywords><keywords scheme="MESH" xml:lang="en"><term>Animals</term><term>Genetic Therapy</term><term>Genetic Vectors</term></keywords><keywords scheme="MESH" xml:lang="fr"><term>Animaux</term><term>Complications postopératoires</term><term>Thérapie génétique</term><term>Vaisseaux lymphatiques</term><term>Vecteurs génétiques</term></keywords></textClass></profileDesc></teiHeader><front><div type="abstract" xml:lang="en">Edema and insufficient blood perfusion are common problems in reconstructive surgery. The blood vasculature is reconstructed in microvascular flaps, whereas lymphatic vessel function is lost after surgical incision. Here, we demonstrate that vascular endothelial growth factor C (VEGF-C) gene transfer can be used to reconstruct a lymphatic vessel network severed by incision of skin flaps. We used adenoviral VEGF-C gene transfer at the edges of epigastric skin flaps in mice. Our results show that VEGF-C gene expression results in the formation of anastomoses between the lymphatic vessels of the skin flap and the surrounding lymphatic vasculature. Some spontaneous lymphangiogenesis also took place in the control mice, but the lymphatic vessels generated remained nonfunctional even 2 months postoperatively. In contrast, the VEGF-C treated mice demonstrated persistent lymphatic vessel function during the 2 month follow-up despite the transient nature of the adenoviral VEGF-C gene expression. The restoration of lymphatic function by VEGF-C in skin flaps provides new tools to promote vascular perfusion and to reduce tissue edema in skin and muscle flaps. These results have important implications for the prevention and treatment of surgically induced secondary lymphedema.</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="Asko Seljavaara, Sirpa" sort="Asko Seljavaara, Sirpa" uniqKey="Asko Seljavaara S" first="Sirpa" last="Asko-Seljavaara">Sirpa Asko-Seljavaara</name><name sortKey="Tammela, Tuomas" sort="Tammela, Tuomas" uniqKey="Tammela T" first="Tuomas" last="Tammela">Tuomas Tammela</name><name sortKey="Timonen, Jari" sort="Timonen, Jari" uniqKey="Timonen J" first="Jari" last="Timonen">Jari Timonen</name><name sortKey="Tukiainen, Erkki" sort="Tukiainen, Erkki" uniqKey="Tukiainen E" first="Erkki" last="Tukiainen">Erkki Tukiainen</name><name sortKey="Yla Herttuala, Seppo" sort="Yla Herttuala, Seppo" uniqKey="Yla Herttuala S" first="Seppo" last="Yla-Herttuala">Seppo Yla-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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