ANGPT1 and Sepsis: First, based on the anti-leakage effect of Ang-1 on mature vasculature [17,52] and the pro-leakage phenotype we have observed with excess Ang-2, we believe Ang-2 is acting as a Tie-2 antagonist in the setting of sepsis as per its initial description [12], but it is worth remembering that the action of Ang-2 on Tie-2 appears to be dose-, duration-, and context-specific in vitro [12,53,54].