Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung
<p>Abstract</p> <p>Background</p> <p>Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the no...
| Main Authors: | , , , |
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| Format: | Article |
| Language: | English |
| Published: |
BMC
2011-01-01
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| Series: | Respiratory Research |
| Online Access: | http://respiratory-research.com/content/12/1/17 |
| _version_ | 1818556054610378752 |
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| author | McLoughlin Paul Costello Christine M Howell Katherine Sands Michelle |
| author_facet | McLoughlin Paul Costello Christine M Howell Katherine Sands Michelle |
| author_sort | McLoughlin Paul |
| collection | DOAJ |
| description | <p>Abstract</p> <p>Background</p> <p>Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF) family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF) and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium.</p> <p>Methods</p> <p>Male Sprague Dawley rats were exposed to conditions of normoxia (21% O<sub>2</sub>) or hypoxia (10% O<sub>2</sub>) for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA), VEGFB, placenta growth factor (PlGF), VEGF receptor 1 (VEGFR1) and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay.</p> <p>Results</p> <p>Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. <it>In vitro </it>PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic.</p> <p>Conclusions</p> <p>VEGFB and PlGF can either inhibit or potentiate the actions of VEGFA, depending on their relative concentrations, which change in the hypoxic lung. Thus their actions <it>in vivo </it>depend on their specific concentrations within the microenvironment of the alveolar wall during the course of adaptation to pulmonary hypoxia.</p> |
| first_indexed | 2024-12-13T23:42:31Z |
| format | Article |
| id | doaj.art-161d5d6026814e0eae3bee905991c6d9 |
| institution | Directory Open Access Journal |
| issn | 1465-9921 |
| language | English |
| last_indexed | 2024-12-13T23:42:31Z |
| publishDate | 2011-01-01 |
| publisher | BMC |
| record_format | Article |
| series | Respiratory Research |
| spelling | doaj.art-161d5d6026814e0eae3bee905991c6d92022-12-21T23:27:07ZengBMCRespiratory Research1465-99212011-01-011211710.1186/1465-9921-12-17Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lungMcLoughlin PaulCostello Christine MHowell KatherineSands Michelle<p>Abstract</p> <p>Background</p> <p>Chronic alveolar hypoxia, due to residence at high altitude or chronic obstructive lung diseases, leads to pulmonary hypertension, which may be further complicated by right heart failure, increasing morbidity and mortality. In the non-diseased lung, angiogenesis occurs in chronic hypoxia and may act in a protective, adaptive manner. To date, little is known about the behaviour of individual vascular endothelial growth factor (VEGF) family ligands in hypoxia-induced pulmonary angiogenesis. The aim of this study was to examine the expression of placenta growth factor (PlGF) and VEGFB during the development of hypoxic pulmonary angiogenesis and their functional effects on the pulmonary endothelium.</p> <p>Methods</p> <p>Male Sprague Dawley rats were exposed to conditions of normoxia (21% O<sub>2</sub>) or hypoxia (10% O<sub>2</sub>) for 1-21 days. Stereological analysis of vascular structure, real-time PCR analysis of vascular endothelial growth factor A (VEGFA), VEGFB, placenta growth factor (PlGF), VEGF receptor 1 (VEGFR1) and VEGFR2, immunohistochemistry and western blots were completed. The effects of VEGF ligands on human pulmonary microvascular endothelial cells were determined using a wound-healing assay.</p> <p>Results</p> <p>Typical vascular remodelling and angiogenesis were observed in the hypoxic lung. PlGF and VEGFB mRNA expression were significantly increased in the hypoxic lung. Immunohistochemical analysis showed reduced expression of VEGFB protein in hypoxia although PlGF protein was unchanged. The expression of VEGFA mRNA and protein was unchanged. <it>In vitro </it>PlGF at high concentration mimicked the wound-healing actions of VEGFA on pulmonary microvascular endothelial monolayers. Low concentrations of PlGF potentiated the wound-healing actions of VEGFA while higher concentrations of PlGF were without this effect. VEGFB inhibited the wound-healing actions of VEGFA while VEGFB and PlGF together were mutually antagonistic.</p> <p>Conclusions</p> <p>VEGFB and PlGF can either inhibit or potentiate the actions of VEGFA, depending on their relative concentrations, which change in the hypoxic lung. Thus their actions <it>in vivo </it>depend on their specific concentrations within the microenvironment of the alveolar wall during the course of adaptation to pulmonary hypoxia.</p>http://respiratory-research.com/content/12/1/17 |
| spellingShingle | McLoughlin Paul Costello Christine M Howell Katherine Sands Michelle Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung Respiratory Research |
| title | Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung |
| title_full | Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung |
| title_fullStr | Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung |
| title_full_unstemmed | Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung |
| title_short | Placenta growth factor and vascular endothelial growth factor B expression in the hypoxic lung |
| title_sort | placenta growth factor and vascular endothelial growth factor b expression in the hypoxic lung |
| url | http://respiratory-research.com/content/12/1/17 |
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