{"id":{"repo_id":"aachen","oai_identifier":"oai:publications.rwth-aachen.de:62211"},"canonical_url":"https://search.dev.ndltd.org/etd/aachen/oai:publications.rwth-aachen.de:62211","repository":{"repo_id":"aachen","name":"RWTH Aachen University","base_url":"https://publications.rwth-aachen.de/oai2d"},"display":{"title":"Systemic overexpression of hVEGF-165 in rat liver impairs glomerular healing in experimental mesangioproliferative nephritis","abstract":"Vascular endothelial growth factor (VEGF) regulates vascular permeability and endothelial cell proliferation. In the rat anti-Thy1.1 mesangioproliferative nephritis inhibition of VEGF-165 impairs glomerular endothelial repair. We now studied the effects of systemic overexpression of hVEGF-165 during glomerular endothelial damage in this model. Hepatic gene transfer was performed by tail vein injection of a human VEGF-165 expression plasmid or LacZ control vector 24 hours prior to induction of anti-Thy1.1-nephritis. Rats receiving high dose VEGF-165 (800 µg plasmid; serum levels at 48h 762+/-434 pg/ml vs. < 30 pg/ml in LacZ rats) showed generalized edema and transient hypotension on days 0 and 1, whereas LacZ treated animals remained normotensive. On days 2 and/or 6 after disease induction, mesangiolysis, glomerular cell proliferation and glomerular monocyte/macrophage infiltration was significantly increased in high dose VEGF-165 rats vs. LacZ rats. Proteinuria on day 6 was 142+/-29 mg/d (VEGF-165) vs. 66+/-41 mg/d (LacZ). Aggravation of glomerular injury was not due to altered anti-Thy1.1 antibody binding after VEGF165 gene transfer. Rather, a dihydralazine treated control group with sham gene transfer showed that systemic hypotension per se augmented glomerular injury. However, hepatic overexpression of 8-fold lower VEGF doses in anti-Thy1.1-nephritis also resulted in augmented damage on day 2 and failed to improve glomerular histology on day 6. In summary, contrary to our expectation, VEGF-165 overexpression during early anti-Thy1.1 nephritis augmented glomerular injury, possibly mediated by systemic hypotension and/or uncoordinated endothelial repair. These findings raise important safety concerns in cases of systemic VEGF therapy and concomittant mesangiolytic injury.","abstract_html":"Vascular endothelial growth factor (VEGF) regulates vascular permeability and endothelial cell proliferation. In the rat anti-Thy1.1 mesangioproliferative nephritis inhibition of VEGF-165 impairs glomerular endothelial repair. We now studied the effects of systemic overexpression of hVEGF-165 during glomerular endothelial damage in this model. Hepatic gene transfer was performed by tail vein injection of a human VEGF-165 expression plasmid or LacZ control vector 24 hours prior to induction of anti-Thy1.1-nephritis. Rats receiving high dose VEGF-165 (800 µg plasmid; serum levels at 48h 762+/-434 pg/ml vs. &lt; 30 pg/ml in LacZ rats) showed generalized edema and transient hypotension on days 0 and 1, whereas LacZ treated animals remained normotensive. On days 2 and/or 6 after disease induction, mesangiolysis, glomerular cell proliferation and glomerular monocyte/macrophage infiltration was significantly increased in high dose VEGF-165 rats vs. LacZ rats. Proteinuria on day 6 was 142+/-29 mg/d (VEGF-165) vs. 66+/-41 mg/d (LacZ). Aggravation of glomerular injury was not due to altered anti-Thy1.1 antibody binding after VEGF165 gene transfer. Rather, a dihydralazine treated control group with sham gene transfer showed that systemic hypotension per se augmented glomerular injury. However, hepatic overexpression of 8-fold lower VEGF doses in anti-Thy1.1-nephritis also resulted in augmented damage on day 2 and failed to improve glomerular histology on day 6. In summary, contrary to our expectation, VEGF-165 overexpression during early anti-Thy1.1 nephritis augmented glomerular injury, possibly mediated by systemic hypotension and/or uncoordinated endothelial repair. These findings raise important safety concerns in cases of systemic VEGF therapy and concomittant mesangiolytic injury.","abstract_has_math":false,"creators":["Rong, Song"],"institution":"Publikationsserver der RWTH Aachen University","degree_name":null,"degree_level":null,"degree_discipline":null,"degree_department":null,"school":null,"contributors":["Flöge, Jürgen"],"advisors":[],"committee_chairs":[],"committee_members":[],"year":2005,"date_issued":"2005","date_published":"2005","updated_at":"2026-07-30T19:43:19Z","subjects":["info:eu-repo/classification/ddc/610","Medizin","Vascular endothelial Growth Factor","Mesangiale Immunglobulin-A-Glomerulonephritis","Gentransfer","Angiogenese","VEGF","mesangioproliferative nephritis","gene transfer","angiogenesis"],"languages":["eng"],"rights":["info:eu-repo/semantics/openAccess"],"rights_urls":[],"identifier_entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123793%22"],"render_values":[{"text":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123793%22","href":"https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123793%22","code":true}]}]},"links":{"outbound_url":"https://publications.rwth-aachen.de/record/62211","outbound_label":"Repository record","outbound_source":"dc:identifier"},"metadata_groups":[{"id":"people","label":"People","entries":[{"key":"dc:contributor","label":"Contributor","values":["Flöge, Jürgen"]},{"key":"dc:creator","label":"Author","values":["Rong, Song"]}]},{"id":"academic_context","label":"Academic Context","entries":[{"key":"dc:coverage","label":"Dc Coverage","values":["DE"]},{"key":"dc:date","label":"Dc Date","values":["2005"]},{"key":"dc:publisher","label":"Institution","values":["Publikationsserver der RWTH Aachen University"]},{"key":"dc:relation","label":"Dc Relation","values":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-13283"]},{"key":"dc:type","label":"Dc Type","values":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]}]},{"id":"subjects_keywords","label":"Subjects and Keywords","entries":[{"key":"dc:subject","label":"Dc Subject","values":["info:eu-repo/classification/ddc/610","Medizin","Vascular endothelial Growth Factor","Mesangiale Immunglobulin-A-Glomerulonephritis","Gentransfer","Angiogenese","VEGF","mesangioproliferative nephritis","gene transfer","angiogenesis"]}]},{"id":"language_rights","label":"Language and Rights","entries":[{"key":"dc:language","label":"Dc Language","values":["eng"]},{"key":"dc:rights","label":"Dc Rights","values":["info:eu-repo/semantics/openAccess"]}]},{"id":"identifiers","label":"Identifiers","entries":[{"key":"dc:identifier","label":"Identifier","values":["https://publications.rwth-aachen.de/record/62211","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123793%22"]}]},{"id":"additional","label":"Additional Metadata","entries":[{"key":"dc:description","label":"Description","values":["Vascular endothelial growth factor (VEGF) regulates vascular permeability and endothelial cell proliferation. In the rat anti-Thy1.1 mesangioproliferative nephritis inhibition of VEGF-165 impairs glomerular endothelial repair. We now studied the effects of systemic overexpression of hVEGF-165 during glomerular endothelial damage in this model. Hepatic gene transfer was performed by tail vein injection of a human VEGF-165 expression plasmid or LacZ control vector 24 hours prior to induction of anti-Thy1.1-nephritis. Rats receiving high dose VEGF-165 (800 µg plasmid; serum levels at 48h 762+/-434 pg/ml vs. < 30 pg/ml in LacZ rats) showed generalized edema and transient hypotension on days 0 and 1, whereas LacZ treated animals remained normotensive. On days 2 and/or 6 after disease induction, mesangiolysis, glomerular cell proliferation and glomerular monocyte/macrophage infiltration was significantly increased in high dose VEGF-165 rats vs. LacZ rats. Proteinuria on day 6 was 142+/-29 mg/d (VEGF-165) vs. 66+/-41 mg/d (LacZ). Aggravation of glomerular injury was not due to altered anti-Thy1.1 antibody binding after VEGF165 gene transfer. Rather, a dihydralazine treated control group with sham gene transfer showed that systemic hypotension per se augmented glomerular injury. However, hepatic overexpression of 8-fold lower VEGF doses in anti-Thy1.1-nephritis also resulted in augmented damage on day 2 and failed to improve glomerular histology on day 6. In summary, contrary to our expectation, VEGF-165 overexpression during early anti-Thy1.1 nephritis augmented glomerular injury, possibly mediated by systemic hypotension and/or uncoordinated endothelial repair. These findings raise important safety concerns in cases of systemic VEGF therapy and concomittant mesangiolytic injury."]},{"key":"dc:source","label":"Dc Source","values":["Aachen : Publikationsserver der RWTH Aachen University 85 S. : Ill., graph. Darst. (2005). = Aachen, Techn. Hochsch., Diss., 2005"]},{"key":"dc:title","label":"Title","values":["Systemic overexpression of hVEGF-165 in rat liver impairs glomerular healing in experimental mesangioproliferative nephritis"]}]}],"canonical_facts":{"dc:contributor":["Flöge, Jürgen"],"dc:coverage":["DE"],"dc:creator":["Rong, Song"],"dc:date":["2005"],"dc:description":["Vascular endothelial growth factor (VEGF) regulates vascular permeability and endothelial cell proliferation. In the rat anti-Thy1.1 mesangioproliferative nephritis inhibition of VEGF-165 impairs glomerular endothelial repair. We now studied the effects of systemic overexpression of hVEGF-165 during glomerular endothelial damage in this model. Hepatic gene transfer was performed by tail vein injection of a human VEGF-165 expression plasmid or LacZ control vector 24 hours prior to induction of anti-Thy1.1-nephritis. Rats receiving high dose VEGF-165 (800 µg plasmid; serum levels at 48h 762+/-434 pg/ml vs. < 30 pg/ml in LacZ rats) showed generalized edema and transient hypotension on days 0 and 1, whereas LacZ treated animals remained normotensive. On days 2 and/or 6 after disease induction, mesangiolysis, glomerular cell proliferation and glomerular monocyte/macrophage infiltration was significantly increased in high dose VEGF-165 rats vs. LacZ rats. Proteinuria on day 6 was 142+/-29 mg/d (VEGF-165) vs. 66+/-41 mg/d (LacZ). Aggravation of glomerular injury was not due to altered anti-Thy1.1 antibody binding after VEGF165 gene transfer. Rather, a dihydralazine treated control group with sham gene transfer showed that systemic hypotension per se augmented glomerular injury. However, hepatic overexpression of 8-fold lower VEGF doses in anti-Thy1.1-nephritis also resulted in augmented damage on day 2 and failed to improve glomerular histology on day 6. In summary, contrary to our expectation, VEGF-165 overexpression during early anti-Thy1.1 nephritis augmented glomerular injury, possibly mediated by systemic hypotension and/or uncoordinated endothelial repair. These findings raise important safety concerns in cases of systemic VEGF therapy and concomittant mesangiolytic injury."],"dc:identifier":["https://publications.rwth-aachen.de/record/62211","https://publications.rwth-aachen.de/search?p=id:%22RWTH-CONV-123793%22"],"dc:language":["eng"],"dc:publisher":["Publikationsserver der RWTH Aachen University"],"dc:relation":["info:eu-repo/semantics/altIdentifier/urn/urn:nbn:de:hbz:82-opus-13283"],"dc:rights":["info:eu-repo/semantics/openAccess"],"dc:source":["Aachen : Publikationsserver der RWTH Aachen University 85 S. : Ill., graph. Darst. (2005). = Aachen, Techn. Hochsch., Diss., 2005"],"dc:subject":["info:eu-repo/classification/ddc/610","Medizin","Vascular endothelial Growth Factor","Mesangiale Immunglobulin-A-Glomerulonephritis","Gentransfer","Angiogenese","VEGF","mesangioproliferative nephritis","gene transfer","angiogenesis"],"dc:title":["Systemic overexpression of hVEGF-165 in rat liver impairs glomerular healing in experimental mesangioproliferative nephritis"],"dc:type":["info:eu-repo/semantics/doctoralThesis","info:eu-repo/semantics/publishedVersion"]},"updated_at":"2026-07-30T19:43:19Z"}