Flow-dependent regulation of endothelial Tie2 by GATA3 in vivo

Abstract Background Reduced endothelial Tie2 expression occurs in diverse experimental models of critical illness, and suppression is sufficient to increase spontaneous vascular permeability. Looking for a common denominator among different illnesses that could drive the same suppressive (thereby leak inducing) phenotype, we identified “circulatory shock” as shared feature postulated flow-dependency gene GATA3 dependent manner. Here, analyzed if this mechanism flow-regulation exists vivo absence inflammation. Results To experimentally mimic shock-like situation, developed murine model clonidine-induced hypotension by targeting reduced mean arterial pressure (MAP) approximately 50% over 4 h. We found hypotension-induced reduction flow confounding disease factors (i.e., inflammation, injury, others) suppress transcription. Conditional endothelial-specific knockdown (B6-Gata3 tm1-Jfz VE-Cadherin(PAC)-cerERT2) led baseline inducing leak. On contrary, transient overexpression pulmonary endothelium (jet-PEI plasmid delivery platform) was at completely block its acute drop. functional level, protection abrogated development capillary leakage. Conclusions The data suggest GATA3–Tie2 signaling pathway might play pivotal role controlling barrier function it affected with shock consequence flow-regulated response. Targeting novel offer therapeutic opportunities treat leakage etiologies.