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Query: UMLS:C0242706 (hyperoxia)
 5,219 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Retinopathy of prematurity (ROP) is initiated by hyperoxia-induced obliteration of newly formed blood vessels in the retina of the premature newborn. We propose that vessel regression is a consequence of hyperoxia-induced withdrawal of a critical vascular survival factor. We show that regression of retinal capillaries in neonatal rats exposed to high oxygen, is preceded by a shut-off of vascular endothelial growth factor (VEGF) production by nearby neuroglial cells. Vessel regression occurs via selective apoptosis of endothelial cells. Intraocular injection of VEGF at the onset of experimental hyperoxia prevents apoptotic death of endothelial cells and rescues the retinal vasculature. These findings provide evidence for a specific angiogenic factor acting as a vascular survival factor in vivo. The system also provides a paradigm for vascular remodelling as an adaptive response to an increase in oxygen tension and suggests a novel approach to prevention of ROP.
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PMID:Vascular endothelial growth factor acts as a survival factor for newly formed retinal vessels and has implications for retinopathy of prematurity. 748 57

Exposure to high levels of inspired oxygen leads to respiratory failure and death in many animal models. Endothelial cell death is an early finding, before the onset of respiratory failure. Vascular endothelial growth factor (VEGF) is highly expressed in the lungs of adult animals. In the present study, adult Sprague-Dawley rats were exposed to >95% FiO2 for 24 or 48 hours. Northern blot analysis revealed a marked reduction in VEGF mRNA abundance by 24 hours, which decreased to less than 50% of control by 48 hours. In situ hybridization revealed that VEGF was highly expressed in distal airway epithelial cells in controls but disappeared in the oxygen-exposed animals. Immunohistochemistry and Western blot analyses demonstrated that VEGF protein was decreased at 48 hours. TUNEL staining demonstrated the presence of apoptotic cells coincident with the decline in VEGF. Abundance of VEGF receptor mRNAs (Flt-1 and KDR/Flk) decreased in the late time points of the study (48 hours), possibly secondary to the loss of endothelial cells. We speculate that VEGF functions as a survival factor in the normal adult rat lung, and its loss during hyperoxia contributes to the pathophysiology of oxygen-induced lung damage.
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PMID:Exposure to hyperoxia decreases the expression of vascular endothelial growth factor and its receptors in adult rat lungs. 1007 60

The goal of this study was to monitor the vascular bed during the lag phase in growth of implanted spheroids as a model of tumor dormancy. Vascular development and tumor growth were followed up by magnetic resonance imaging in a model system of MLS ovarian carcinoma spheroids implanted subcutaneously in female nude mice. Apparent vessel density in a 1-mm rim surrounding the spheroid was evaluated by gradient echo imaging as a measure of the angiogenic potential of the tumor. Vascular functionality and maturation were assessed by signal intensity changes in response to hyperoxia (elevated oxygen) and hypercapnia (elevated carbon dioxide), respectively. Tumor growth was delayed by 12 to 57 days after implantation. During this long period in which tumor volume did not change, up to 6 cycles of vascular development and regression were observed. We propose here that dynamic remodeling of the vascular bed may precede exit of tumors from dormancy. The sustained oscillations in the angiogenic response to the implanted spheroid are consistent with hypoxic regulation of vascular endothelial growth factor (VEGF), combined with the role of VEGF as an essential survival factor for newly formed blood vessels. Vascular maturation, manifested by physiological vasodilatory response to carbon dioxide, may be important for conferring vascular stability and exit from dormancy.
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PMID:Dynamic remodeling of the vascular bed precedes tumor growth: MLS ovarian carcinoma spheroids implanted in nude mice. 1093 77

Development of microvascular networks is set to meet the metabolic requirements of the tissue they perfuse. Accordingly, impairment of oxygen homeostasis, either due to increased oxygen consumption or as a result of blood vessel occlusion, triggers compensatory neovascularization. This feedback reaction is mediated by a hypoxia- and hypoglycemia-induced vascular endothelial growth factor (VEGF). VEGF accumulates under stress as a result of increased hypoxia-inducible factor-1alpha-mediated transcription, stabilization of the mRNA, and the function of a hypoxia-refractory internal ribosome entry site within its 5'-untranslated region. Matching of vascular density to the metabolic needs of the tissue may include a process of hyperoxia-induced vessel regression. Thus newly formed vascular networks may undergo a natural process of vascular pruning that takes place whenever VEGF, acting as a vascular survival factor, is downregulated below the level required to sustain immature vessels. Immature vessels are particularly vulnerable and are selectively obliterated upon withdrawal of VEGF. The plasticity window for vessel regression is determined by a delay in the recruitment of periendothelial cells to the preformed endothelial plexus. Thus fine-tuning of microvascular density takes place mostly in the newly formed plexus, but the mature system is refractory to episodic changes in tissue oxygenation. These regulatory links may malfunction in certain pathological settings.
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PMID:Vascular endothelial growth factor and vascular adjustments to perturbations in oxygen homeostasis. 1135 Jul 31

In mice the retinal vasculature develops in the first postnatal week by spreading from the optic nerve head towards the retinal periphery. During this growth period, exposure to hyperoxia causes vaso-obliteration of capillaries in the retinal center but not in peripheral regions. High oxygen levels lead to downregulation of vascular endothelial growth factor (VEGF), an important survival factor for vascular endothelial cells, which could explain the vaso-obliteration caused by hyperoxia. However, it is not clear why only capillaries in the center of the retina are affected. We therefore investigated how capillary obliteration correlates with VEGF mRNA distribution by in situ hybridization in retinal whole mount preparations. In mouse pups reared under normoxic conditions VEGF mRNA was detectable across the entire vascular network but was virtually absent in the immediate vicinity of arteries. This was true along developing retinal arteries but also around the optic nerve head through which the entire arterial blood supply for the retinal and hyaloid vasculature passes. In these areas capillaries were absent, resulting in so-called capillary free zones. Exposure to hyperoxia caused an expansion of areas with low VEGF mRNA which correlated with capillary obliteration in these regions. Combined capillary obliteration around the optic nerve head and along retinal arteries lead to a large capillary free zone in the center of the retina. Thus, our observations suggest that hyperoxia affects the retinal vasculature by reducing VEGF mRNA levels near arteries and causing a widening of capillary free zones.
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PMID:Role of arteries in oxygen induced vaso-obliteration. 1290 63

The pulmonary vascular endothelial cell plays a crucial role in the regulation of the pulmonary vascular tone and in the maintenance of the barrier function and integrity of the alveolar-capillary membrane. It also plays a major role in coagulation, fibrinolysis, and angiogenesis and participates in inflammatory reactions. Vascular endothelial growth factor (VEGF) is a central growth and survival factor for the endothelial cell. Particularly high levels of VEGF are expressed in the lungs, reflecting the critical role of VEGF for lung development and structural integrity of the adult lung. Vascular endothelial growth factor exerts a variety of physiological and pathophysiological actions in the lung. Recent evidence suggests its involvement in the pathogenesis of lung diseases such as bronchopulmonary dysplasia, acute lung injury, emphysema, and pulmonary hypertension. To summarize the critical effects of VEGF on the pulmonary endothelial cell in the pathogenesis of these diseases, the purposes of this review are to (1) discuss the biological activities and intracellular signaling pathways of VEGF in the lung; (2) summarize the regulatory mechanisms involved in VEGF expression; (3)address the effects of VEGF on endothelial cells in hyperoxia-induced and other forms of lung injury; (4) highlight the endothelial effects of VEGF in the pathogenesis of emphysema; and (5) explore the role of VEGF in the pathogenesis of pulmonary arterial hypertension.
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PMID:The critical role of vascular endothelial growth factor in pulmonary vascular remodeling after lung injury. 1751 May 98