Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Pivot Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Target Concepts:
Gene/Protein
Disease
Symptom
Drug
Enzyme
Compound
Query: UMLS:C0034063 (
pulmonary edema
)
10,665
document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)
Sepsis and septic shock are among the most common causes of death in the intensive care unit; advanced therapeutic approaches are thus urgently needed. Vascular hyperpermeability represents a major manifestation of severe sepsis and is responsible for the ensuing organ dysfunction and failure. Vasopressin V
1A
receptor (V
1A
R) agonists have shown promise in the treatment of sepsis, increasing blood pressure, and reducing vascular hyperpermeability. The effects of the selective V
1A
R-selective agonist selepressin have been investigated in an in vitro model of thrombin-, vascular endothelial growth factor-, angiopoietin 2-, and lipopolysaccharide (LPS)-induced pulmonary microvascular endothelial hyperpermeability. Results suggest that selepressin counteracts the effects of all four endothelial barrier disruptors in a concentration-dependent manner, as reflected in real-time measurements of vascular permeability by means of transendothelial electrical resistance. Further, selepressin protected the barrier integrity against the LPS-mediated corruption of the endothelial monolayer integrity, as captured by
VE-cadherin
and actin staining. The protective effects of selepressin were abolished by silencing of the vasopressin V
1A
R, as well as by atosiban, an antagonist of the human V
1A
R. p53 appears to be involved in mediating these palliative effects, since selepressin strongly induced its expression levels, suppressed the inflammatory RhoA/myosin light chain2 pathway, and triggered the barrier-protective effects of the GTPase Rac1. We conclude that V
1A
R-selective agonists, such as selepressin, may prove useful in the improvement of endothelial barrier function in the management of severe sepsis. SIGNIFICANCE STATEMENT: A cardinal sign of sepsis, a serious disease with significant mortality and no specific treatment, is pulmonary endothelial barrier dysfunction that leads to
pulmonary edema
. Here, we present evidence that in cultured human lung microvascular endothelial cells, the synthetic, selective vasopressin V
1A
receptor agonist selepressin protects against endothelial barrier dysfunction caused by four different edemogenic agents, suggesting a potential role of selepressin in the clinical management of sepsis.
...
PMID:Protective Mechanism of the Selective Vasopressin V
1A
Receptor Agonist Selepressin against Endothelial Barrier Dysfunction. 3294 78
<< Previous
1
2
3
4
5
6
7
