Tie2 protects the vasculature against thrombus formation in systemic inflammation

Serum Angiopoietin‐2 Predicts Mortality and Kidney Outcomes in Decompensated Cirrhosis

“…As a cell‐surface receptor modulated by secreted ligands, Tie2 and Angiopoietins constitute a highly promising set of candidate drug targets for human disease. In experimental models of sepsis, systemic inflammatory syndrome, and disseminated intravascular coagulation, Angpt‐2 upregulation and Tie2 inhibition have been linked to thrombocytopenia, increased INR, elevated D‐dimer, overexpression of pro‐inflammatory cytokines, multisystem organ dysfunction (e.g., AKI), decreased systemic circulating blood pressure, and ultimately poorer survival; conversely, interventions to restore or enhance Tie2 signaling not only ameliorate these abnormalities but also improve survival . Strikingly, this same constellation of features is present among patients with decompensated cirrhosis and ACLF .…”

“…When activated, Tie2 signaling fortifies interendothelial junctions and reduces the expression of leukocyte adhesion molecules . Angiopoietin‐2 (Angpt‐2) is a context‐specific antagonist of the Tie2 receptor that potentiates permeability and vascular inflammation by weakening adherens junctions, recruiting inflammatory cells, and promoting dysregulated thrombosis in the microvasculature . Targeted manipulations of Angiopoietin/Tie2 signaling—whether by genetic approaches, antibodies, or RNA interference, reported by independent groups—consistently implicate excess Angpt‐2 in the end‐organ injury and hemodynamic alterations that arise in experimental sepsis and liver disease .…”

Thrombotic Regulation From the Endothelial Cell Perspectives

“…18 Indeed, endothelium-derived TF functionally participates in thrombosis. [19][20][21][22][23][24] In this regard, Witkowski et al 25 identified that circulating miR-126, which was primarily produced by ECs, 26 attenuated thrombosis via decreasing the expression of both mRNA and protein of TF. Their study showed that levels of plasma miR-126 were negatively correlated with concentrations and activities of plasma TF in diabetic patients.…”

How we manage haemostasis during sepsis

“…Critically, Tie2 activation had no adverse effects on bleeding. These results mechanistically implicate Tie2 signalling as a central regulator of microvascular thrombus formation in septic DIC and indicate that circulating markers of the Tie2 axis could facilitate earlier diagnosis (Higgins et al , ).…”

“…However, disruption of the endothelial Tie2 axis maybe central in septic DIC. Angiopoietin‐2, a Tie2 antagonist, was strongly associated with traditional DIC markers including platelet counts, yet more accurately predicted mortality utilising samples from two large independent cohorts (combined N = 1077) (Higgins et al , ). Furthermore, in endotoxemic mice, reduced Tie2 signalling preceded signs of overt DIC.…”