Female sex protects against renal edema, but not lung edema, in mice with partial deletion of the endothelial barrier regulator Tie2 compared to male sex

The endothelial angiopoietin/Tie2 system is an important regulator of endothelial permeability and targeting Tie2 reduces hemorrhagic shock-induced organ edema in males. However, sexual dimorphism of the endothelium has not been taken into account. This study investigated whether there are sex-relat...

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Vydáno v:PloS one Ročník 18; číslo 11; s. e0293673
Hlavní autoři: van Leeuwen, Anoek L. I., Beijer, Elise, Ibelings, Roselique, Dekker, Nicole A. M., van der Steen, Marjolein R. A., Roelofs, Joris J. T. H., van Meurs, Matijs, Molema, Grietje, van den Brom, Charissa E.
Médium: Journal Article
Jazyk:angličtina
Vydáno: San Francisco Public Library of Science 16.11.2023
Public Library of Science (PLoS)
Témata:
Angiopoietin
Animals
Circulation
Deletion
Demographic aspects
Diagnosis
Dropsy
Dry weight
Edema
Endothelium
Enzyme-linked immunosorbent assay
Estrogen
Estrogen receptors
Estrogens
Ethylenediaminetetraacetic acid
Experiments
Females
Gender differences
Gene expression
Genes
Hemorrhagic shock
Kidneys
Kinases
Lungs
Males
Neutrophils
Permeability
Phosphatase
Phosphorylation
Proteins
R&D
Renal agenesis
Research & development
Risk factors
RNA
Sex differences
Sexual dimorphism
Vascular endothelial growth factor
Weight
Netherlands
Minneapolis Minnesota
United States > US
ISSN:1932-6203, 1932-6203
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Shrnutí:The endothelial angiopoietin/Tie2 system is an important regulator of endothelial permeability and targeting Tie2 reduces hemorrhagic shock-induced organ edema in males. However, sexual dimorphism of the endothelium has not been taken into account. This study investigated whether there are sex-related differences in the endothelial angiopoietin/Tie2 system and edema formation. Adult male and female heterozygous Tie2 knockout mice (Tie2.sup.+/-) and wild-type controls (Tie2.sup.+/+) were included (n = 9 per group). Renal and pulmonary injury were determined by wet/dry weight ratio and H&E staining of tissue sections. Protein levels were studied in plasma by ELISA and pulmonary and renal mRNA expression levels by RT-qPCR. In Tie2.sup.+/+ mice, females had higher circulating angiopoietin-2 (138%, p<0.05) compared to males. Gene expression of angiopoietin-1 (204%, p<0.01), angiopoietin-2 (542%, p<0.001) were higher in females compared to males in kidneys, but not in lungs. Gene expression of Tie2, Tie1 and VE-PTP were similar between males and females in both organs. Renal and pulmonary wet/dry weight ratio did not differ between Tie2.sup.+/+ females and males. Tie2.sup.+/+ females had lower circulating NGAL (41%, p<0.01) compared to males, whereas renal NGAL and KIM1 gene expression was unaffected. Female sex seems to protect against renal, but not pulmonary edema in heterozygous Tie2 knock-out mice. This could not be explained by sex dimorphism in the endothelial angiopoietin/Tie2 system.
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ISSN:1932-6203
1932-6203
DOI:10.1371/journal.pone.0293673