| Cell-based gene transfer of vascular endothelial growth factor attenuates monocrotaline-induced pulmonary hypertension. | |
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MedLine Citation:
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PMID: 11684638 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Pulmonary arterial hypertension is characterized by increased pulmonary vascular resistance secondary to a decrease in the caliber and number of pulmonary vascular channels. We hypothesized that the targeted overexpression of an angiogenic factor within the lung would potentially minimize the development and progression of pulmonary arterial hypertension by preventing the loss of existing vessels or by inducing the development of new blood vessels within the lung. METHODS AND RESULTS: We used a cell-based method of gene transfer to the pulmonary microvasculature by delivering syngeneic smooth muscle cells overexpressing vascular endothelial growth factor (VEGF)-A to inbred Fisher 344 rats in which pulmonary hypertension was induced with the pulmonary endothelial toxin monocrotaline. Four weeks after simultaneous endothelial injury and cell-based gene transfer, right ventricular (RV) hypertension and RV and vascular hypertrophy were significantly decreased in the VEGF-treated animals. Four weeks after gene transfer, the plasmid VEGF transcript was still detectable in the pulmonary tissue of animals injected with VEGF-transfected cells, demonstrating survival of the transfected cells and persistent transgene expression. In addition, delay of cell-based gene transfer until after the development of pulmonary hypertension also resulted in a significant decrease in the progression of RV hypertension and hypertrophy. CONCLUSIONS: These results indicate that cell-based VEGF gene transfer is an effective method of preventing the development and progression of pulmonary hypertension in the monocrotaline model and suggest a potential therapeutic role for angiogenic factors in the therapy of this devastating disease. |
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Authors:
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A I Campbell; Y Zhao; R Sandhu; D J Stewart |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't |
Journal Detail:
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Title: Circulation Volume: 104 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2001 Oct |
Date Detail:
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Created Date: 2001-10-30 Completed Date: 2001-12-04 Revised Date: 2006-11-15 |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 2242-8 Citation Subset: AIM; IM |
Affiliation:
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Division of Cardiac Surgery, University of Toronto, Terrence Donnelly Heart Centre, St Michael's Hospital, Toronto, Ontario, Canada. |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Animals Cell Transplantation / methods Cells, Cultured Disease Models, Animal Endothelial Growth Factors / administration & dosage*, biosynthesis, genetics Fluorescent Dyes Gene Therapy / methods* Gene Transfer Techniques Hypertension, Pulmonary / chemically induced, pathology, therapy* Lung / blood supply, drug effects*, pathology Lymphokines / administration & dosage*, biosynthesis, genetics Microcirculation / drug effects Monocrotaline Muscle, Smooth, Vascular / cytology, metabolism, transplantation* Pulmonary Circulation / drug effects, genetics Rats Rats, Inbred F344 Transplantation, Isogeneic Treatment Outcome Vascular Endothelial Growth Factor A Vascular Endothelial Growth Factors |
| Chemical | |
Reg. No./Substance:
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0/Endothelial Growth Factors; 0/Fluorescent Dyes; 0/Lymphokines; 0/Vascular Endothelial Growth Factor A; 0/Vascular Endothelial Growth Factors; 315-22-0/Monocrotaline |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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