Abstract
Vascular endothelial growth factor (VEGF) is a potent mediator of capillary leak if it gains access to its receptors on the capillary endothelium. We have observed that there are high levels of VEGF compartmentalized in the alveolar epithelial lining fluid of normal humans at levels 500-fold greater than plasma. The potential for high altitude to result in compromise of alveolar epithelial tight junctions and experimental animal studies in which pulmonary edema is induced when VEGF is overexpressed in the alveolar epithelium, suggest a mechanism. We hypothesize that when the epithelial barrier is compromised at high altitude the normally high level of VEGF in the alveolar epithelial fluid has access to the pulmonary endothelium, where it acutely alters permeability, markedly exacerbating the high permeability pulmonary edema that characterizes high altitude pulmonary edema. If correct, this paradigm opens the possibility of testing available anti-VEGF therapies to treat this potentially fatal disorder.
| Original language | English |
|---|---|
| Pages (from-to) | 399-409 |
| Number of pages | 11 |
| Journal | High Altitude Medicine and Biology |
| Volume | 5 |
| Issue number | 4 |
| DOIs | |
| Publication status | Published - 1 Dec 2004 |
| Externally published | Yes |
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Keywords
- Animal models
- Blood-gas barrier or barrier function
- Bronchoalveolar lavage
- Lung
- Molecular pathophysiology
- Permeability
ASJC Scopus subject areas
- Medicine(all)
- Physiology
- Public Health, Environmental and Occupational Health
Cite this
Pathogenesis of high altitude pulmonary edema : Does alveolar epithelial lining fluid vascular endothelial growth factor exacerbate capillary leak? / Kaner, Robert J.; Crystal, Ronald.
In: High Altitude Medicine and Biology, Vol. 5, No. 4, 01.12.2004, p. 399-409.Research output: Contribution to journal › Article
}
TY - JOUR
T1 - Pathogenesis of high altitude pulmonary edema
T2 - Does alveolar epithelial lining fluid vascular endothelial growth factor exacerbate capillary leak?
AU - Kaner, Robert J.
AU - Crystal, Ronald
PY - 2004/12/1
Y1 - 2004/12/1
N2 - Vascular endothelial growth factor (VEGF) is a potent mediator of capillary leak if it gains access to its receptors on the capillary endothelium. We have observed that there are high levels of VEGF compartmentalized in the alveolar epithelial lining fluid of normal humans at levels 500-fold greater than plasma. The potential for high altitude to result in compromise of alveolar epithelial tight junctions and experimental animal studies in which pulmonary edema is induced when VEGF is overexpressed in the alveolar epithelium, suggest a mechanism. We hypothesize that when the epithelial barrier is compromised at high altitude the normally high level of VEGF in the alveolar epithelial fluid has access to the pulmonary endothelium, where it acutely alters permeability, markedly exacerbating the high permeability pulmonary edema that characterizes high altitude pulmonary edema. If correct, this paradigm opens the possibility of testing available anti-VEGF therapies to treat this potentially fatal disorder.
AB - Vascular endothelial growth factor (VEGF) is a potent mediator of capillary leak if it gains access to its receptors on the capillary endothelium. We have observed that there are high levels of VEGF compartmentalized in the alveolar epithelial lining fluid of normal humans at levels 500-fold greater than plasma. The potential for high altitude to result in compromise of alveolar epithelial tight junctions and experimental animal studies in which pulmonary edema is induced when VEGF is overexpressed in the alveolar epithelium, suggest a mechanism. We hypothesize that when the epithelial barrier is compromised at high altitude the normally high level of VEGF in the alveolar epithelial fluid has access to the pulmonary endothelium, where it acutely alters permeability, markedly exacerbating the high permeability pulmonary edema that characterizes high altitude pulmonary edema. If correct, this paradigm opens the possibility of testing available anti-VEGF therapies to treat this potentially fatal disorder.
KW - Animal models
KW - Blood-gas barrier or barrier function
KW - Bronchoalveolar lavage
KW - Lung
KW - Molecular pathophysiology
KW - Permeability
UR - http://www.scopus.com/inward/record.url?scp=14644415579&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=14644415579&partnerID=8YFLogxK
U2 - 10.1089/ham.2004.5.399
DO - 10.1089/ham.2004.5.399
M3 - Article
C2 - 15671629
AN - SCOPUS:14644415579
VL - 5
SP - 399
EP - 409
JO - High Altitude Medicine and Biology
JF - High Altitude Medicine and Biology
SN - 1527-0297
IS - 4
ER -