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Partial Deletion of Tie2 Affects Microvascular Endothelial Responses to Critical Illness in A Vascular Bed and Organ-Specific Way.
- Source :
-
Shock (Augusta, Ga.) [Shock] 2019 Jun; Vol. 51 (6), pp. 757-769. - Publication Year :
- 2019
-
Abstract
- Tyrosine kinase receptor (Tie2) is mainly expressed by endothelial cells. In animal models mimicking critical illness, Tie2 levels in organs are temporarily reduced. Functional consequences of these reduced Tie2 levels on microvascular endothelial behavior are unknown. We investigated the effect of partial deletion of Tie2 on the inflammatory status of endothelial cells in different organs. Newly generated heterozygous Tie2 knockout mice (exon 9 deletion, ΔE9/Tie2) exhibiting 50% reduction in Tie2 mRNA and protein, and wild-type littermate controls (Tie2), were subjected to hemorrhagic shock and resuscitation (HS + R), or challenged with i.p. lipopolysaccharide (LPS). Kidney, liver, lung, heart, brain, and intestine were analyzed for mRNA levels of adhesion molecules E-selectin, vascular cell adhesion molecule 1 (VCAM-1), and intercellular cell adhesion molecule 1 (ICAM-1), and CD45. Exposure to HS + R did not result in different expression responses of these molecules between organs from Tie2 or Tie2 mice and sham-operated mice. In contrast, the LPS-induced mRNA expression levels of E-selectin, VCAM-1, and ICAM-1, and CD45 in organs were attenuated in Tie2 mice when compared with Tie2 mice in kidney and liver, but not in the other organs studied. Furthermore, reduced expression of E-selectin and VCAM-1 protein, and reduced influx of CD45 cells upon LPS exposure, was visible in a microvascular bed-specific pattern in kidney and liver of Tie2 mice compared with controls. In contrast to the hypothesis that a disbalance in the Ang/Tie2 system leads to increased microvascular inflammation, heterozygous deletion of Tie2 is associated with an organ-restricted, microvascular bed-specific attenuation of endothelial inflammatory response to LPS.
- Subjects :
- Animals
E-Selectin genetics
E-Selectin metabolism
Endothelial Cells pathology
Inflammation chemically induced
Inflammation genetics
Inflammation metabolism
Inflammation pathology
Intercellular Adhesion Molecule-1 genetics
Intercellular Adhesion Molecule-1 metabolism
Leukocyte Common Antigens genetics
Leukocyte Common Antigens metabolism
Lipopolysaccharides toxicity
Mice
Mice, Knockout
Microvessels pathology
Organ Specificity
Receptor, TIE-2 genetics
Vascular Cell Adhesion Molecule-1 genetics
Vascular Cell Adhesion Molecule-1 metabolism
Endothelial Cells metabolism
Microvessels metabolism
Receptor, TIE-2 metabolism
Subjects
Details
- Language :
- English
- ISSN :
- 1540-0514
- Volume :
- 51
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Shock (Augusta, Ga.)
- Publication Type :
- Academic Journal
- Accession number :
- 30520765
- Full Text :
- https://doi.org/10.1097/SHK.0000000000001226