Hypoxia-induced modulation of endothelial cell properties

Regulation of barrier function and expression of interleukin-6

Shi Fang Yan, Satoshi Ogawa, David Stern, David J. Pinsky

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

The endothelial cell response to hypoxia involves a range of adaptive mechanisms that reflect an active response of the cell's biosynthetic and metabolic apparatus. Hypoxia-mediated suppression of endothelial barrier function, resulting in increased vascular leakage, is likely to contribute to pulmonary and cerebral edema associated with high altitude and is closely associated with a fall in intracellular cyclic AMP levels. Buttressing of this second messenger pathway in the endothelium using membrane permeant cyclic AMP analogs prevents increased vascular leakage due to hypoxia. Application of this principle to organ preservation has shown that supplementation with cyclic AMP analogs or inhibition of endogenous cAMP metabolism enables extension of the time a harvested organ can remain extracorporeally, after which transplantation is successful. The underlying mechanism through which cyclic AMP exerts its effects appears to be maintenance of vascular homeostasis in the graft. A distinct adaptive mechanism triggered in the endothelium by hypoxia is expression of the cytokine interleukin-6 (IL-6) by a novel mechanism involving transcription driven by the nuclear factor IL-6 (NF-IL-6) DNA binding site in the promoter. IL-6 may exert protective effects on vascular function, thereby limiting vascular injury by a different mechanism than those recruited by elevated cAMP levels. These studies provide insights into two independent mechanisms through which endothelium responds to oxygen deprivation, and suggest possible new approaches to attentuate vascular injury associated with ischemia.

Original languageEnglish (US)
Pages (from-to)419-425
Number of pages7
JournalKidney International
Volume51
Issue number2
DOIs
StatePublished - Jan 1 1997
Externally publishedYes

Fingerprint

Cyclic AMP
Blood Vessels
Interleukin-6
Endothelial Cells
Endothelium
Vascular System Injuries
CCAAT-Enhancer-Binding Protein-beta
Organ Preservation
Brain Edema
Second Messenger Systems
Pulmonary Edema
Homeostasis
Ischemia
Transplantation
Binding Sites
Maintenance
Cytokines
Oxygen
Transplants
Membranes

All Science Journal Classification (ASJC) codes

  • Nephrology

Cite this

Hypoxia-induced modulation of endothelial cell properties : Regulation of barrier function and expression of interleukin-6. / Yan, Shi Fang; Ogawa, Satoshi; Stern, David; Pinsky, David J.

In: Kidney International, Vol. 51, No. 2, 01.01.1997, p. 419-425.

Research output: Contribution to journalArticle

@article{157a3c9a9fae469aaa1b1682fea18665,
title = "Hypoxia-induced modulation of endothelial cell properties: Regulation of barrier function and expression of interleukin-6",
abstract = "The endothelial cell response to hypoxia involves a range of adaptive mechanisms that reflect an active response of the cell's biosynthetic and metabolic apparatus. Hypoxia-mediated suppression of endothelial barrier function, resulting in increased vascular leakage, is likely to contribute to pulmonary and cerebral edema associated with high altitude and is closely associated with a fall in intracellular cyclic AMP levels. Buttressing of this second messenger pathway in the endothelium using membrane permeant cyclic AMP analogs prevents increased vascular leakage due to hypoxia. Application of this principle to organ preservation has shown that supplementation with cyclic AMP analogs or inhibition of endogenous cAMP metabolism enables extension of the time a harvested organ can remain extracorporeally, after which transplantation is successful. The underlying mechanism through which cyclic AMP exerts its effects appears to be maintenance of vascular homeostasis in the graft. A distinct adaptive mechanism triggered in the endothelium by hypoxia is expression of the cytokine interleukin-6 (IL-6) by a novel mechanism involving transcription driven by the nuclear factor IL-6 (NF-IL-6) DNA binding site in the promoter. IL-6 may exert protective effects on vascular function, thereby limiting vascular injury by a different mechanism than those recruited by elevated cAMP levels. These studies provide insights into two independent mechanisms through which endothelium responds to oxygen deprivation, and suggest possible new approaches to attentuate vascular injury associated with ischemia.",
author = "Yan, {Shi Fang} and Satoshi Ogawa and David Stern and Pinsky, {David J.}",
year = "1997",
month = "1",
day = "1",
doi = "10.1038/ki.1997.56",
language = "English (US)",
volume = "51",
pages = "419--425",
journal = "Kidney International",
issn = "0085-2538",
publisher = "Nature Publishing Group",
number = "2",

}

TY - JOUR

T1 - Hypoxia-induced modulation of endothelial cell properties

T2 - Regulation of barrier function and expression of interleukin-6

AU - Yan, Shi Fang

AU - Ogawa, Satoshi

AU - Stern, David

AU - Pinsky, David J.

PY - 1997/1/1

Y1 - 1997/1/1

N2 - The endothelial cell response to hypoxia involves a range of adaptive mechanisms that reflect an active response of the cell's biosynthetic and metabolic apparatus. Hypoxia-mediated suppression of endothelial barrier function, resulting in increased vascular leakage, is likely to contribute to pulmonary and cerebral edema associated with high altitude and is closely associated with a fall in intracellular cyclic AMP levels. Buttressing of this second messenger pathway in the endothelium using membrane permeant cyclic AMP analogs prevents increased vascular leakage due to hypoxia. Application of this principle to organ preservation has shown that supplementation with cyclic AMP analogs or inhibition of endogenous cAMP metabolism enables extension of the time a harvested organ can remain extracorporeally, after which transplantation is successful. The underlying mechanism through which cyclic AMP exerts its effects appears to be maintenance of vascular homeostasis in the graft. A distinct adaptive mechanism triggered in the endothelium by hypoxia is expression of the cytokine interleukin-6 (IL-6) by a novel mechanism involving transcription driven by the nuclear factor IL-6 (NF-IL-6) DNA binding site in the promoter. IL-6 may exert protective effects on vascular function, thereby limiting vascular injury by a different mechanism than those recruited by elevated cAMP levels. These studies provide insights into two independent mechanisms through which endothelium responds to oxygen deprivation, and suggest possible new approaches to attentuate vascular injury associated with ischemia.

AB - The endothelial cell response to hypoxia involves a range of adaptive mechanisms that reflect an active response of the cell's biosynthetic and metabolic apparatus. Hypoxia-mediated suppression of endothelial barrier function, resulting in increased vascular leakage, is likely to contribute to pulmonary and cerebral edema associated with high altitude and is closely associated with a fall in intracellular cyclic AMP levels. Buttressing of this second messenger pathway in the endothelium using membrane permeant cyclic AMP analogs prevents increased vascular leakage due to hypoxia. Application of this principle to organ preservation has shown that supplementation with cyclic AMP analogs or inhibition of endogenous cAMP metabolism enables extension of the time a harvested organ can remain extracorporeally, after which transplantation is successful. The underlying mechanism through which cyclic AMP exerts its effects appears to be maintenance of vascular homeostasis in the graft. A distinct adaptive mechanism triggered in the endothelium by hypoxia is expression of the cytokine interleukin-6 (IL-6) by a novel mechanism involving transcription driven by the nuclear factor IL-6 (NF-IL-6) DNA binding site in the promoter. IL-6 may exert protective effects on vascular function, thereby limiting vascular injury by a different mechanism than those recruited by elevated cAMP levels. These studies provide insights into two independent mechanisms through which endothelium responds to oxygen deprivation, and suggest possible new approaches to attentuate vascular injury associated with ischemia.

UR - http://www.scopus.com/inward/record.url?scp=0031018716&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0031018716&partnerID=8YFLogxK

U2 - 10.1038/ki.1997.56

DO - 10.1038/ki.1997.56

M3 - Article

VL - 51

SP - 419

EP - 425

JO - Kidney International

JF - Kidney International

SN - 0085-2538

IS - 2

ER -