Fig 1.
Schematic overview of the effect of angiopoietin/Tie2 signaling on endothelial barrier function.
In quiescence (A), angiopoietin-1 (ang-1) is released from pericytes and activates, and thereby phosphorylates tyrosine kinase receptor Tie2. Activation of Tie2 strengthens endothelial barrier function via Rac-1/Rho kinase/vascular endothelial (VE)-cadherin signaling. In contrast, in response to hemorrhagic shock (B) angiopoietin-2 (ang-2) is rapidly released from weibel palade bodies (WPB), leading to increased endothelial permeability via inhibition of Tie2 activation. Other transmembrane proteins that affect Tie2 phosphorylation include Tie1 and vascular endothelial-protein tyrosine phosphatase (VE-PTP), which both inhibit Tie2 phosphorylation upon a stress stimulus.
Table 1.
Real time-qPCR primers.
Fig 2.
Circulating markers of the endothelial angiopoietin/Tie2 system.
Circulating levels of angiopoietin-1 (A), angiopoietin-2 (B), angiopoietin-2/1 ratio (C) and soluble Tie2 (D) in plasma of Tie2+/+ male (white bars), Tie2+/+ female (grey bars), Tie2+/- male (striped white bars) and Tie2+/- female (striped grey bars) mice. Each dot represents an individual mouse. Data are presented as median with interquartile range. * p<0.05, ** p<0.01, *** p<0.001.
Fig 3.
Renal gene expression of the endothelial angiopoietin/Tie2 system.
Renal gene expression of angiopoietin-1 (A), angiopoietin-2 (B), Tie2 (C), Tie1 (D) and vascular endothelial protein tyrosine phosphatase (VE-PTP; E) in Tie2+/+ male (white bars), Tie2+/+ female (grey bars), Tie2+/- male (striped white bars) and Tie2+/- female (striped grey bars) mice. Each dot represents an individual mouse. Data are presented as median with interquartile range. * p<0.05, ** p<0.01, *** p<0.001.
Fig 4.
Pulmonary gene expression of the endothelial angiopoietin/Tie2 system.
Pulmonary gene expression of angiopoietin-1 (A), angiopoietin-2 (B), Tie2 (C), Tie1 (D) and vascular endothelial protein tyrosine phosphatase (VE-PTP; E) in Tie2+/+ male (white bars), Tie2+/+ female (grey bars), Tie2+/- male (striped white bars) and Tie2+/- female (striped grey bars) mice. Each dot represents an individual mouse. Data are presented as median with interquartile range.
Fig 5.
Sex differences and effect of Tie2 heterozygosity in renal and pulmonary function.
Renal wet/dry weight ratio (A), pulmonary wet/dry weight ratio (B), H&E stainings of one typical example of each group in kidney (C) and lung (D), circulating plasma levels of neutrophil gelatinase-associated lipocalin (NGAL; E) and renal gene expression of NGAL (F) and kidney injury molecule 1 (KIM1; G) in Tie2+/+ male (white bars), Tie2+/+ female (grey bars), Tie2+/- male (striped white bars) and Tie2+/- female (striped grey bars) mice. Each dot represents an individual mouse. Data are presented as median with interquartile range. * p<0.05, ** p<0.01, *** p<0.001.
Fig 6.
Renal gene expression of other endothelial barrier regulators.
Renal gene expression of estrogen receptor α (A), estrogen receptor β (B), integrin α5 (C), integrin β1 (D), vascular endothelial growth factor α (VEGFα; E), RhoA (F) and Rac1 (G) in Tie2+/+ male (white bars), Tie2+/+ female (grey bars), Tie2+/- male (striped white bars) and Tie2+/- female (striped grey bars) mice. Each dot represents an individual mouse. Data are presented as median with interquartile range. * p<0.05, *** p<0.001.
Fig 7.
Pulmonary gene expression of other endothelial barrier regulators.
Pulmonary gene expression of estrogen receptor α (A), estrogen receptor β (B), integrin α5 (C), integrin β1 (D), vascular endothelial growth factor α (VEGFα; E), RhoA (F) and Rac1 (G) in Tie2+/+ male (white bars), Tie2+/+ female (grey bars), Tie2+/- male (striped white bars) and Tie2+/- female (striped grey bars) mice. Each dot represents an individual mouse. Data are presented as median with interquartile range. ** p<0.01.