Figure 1.

Model of damage-associated molecular pattern (DAMP)- and extracellular vesicle (EV)-induced secondary organ failure (SOF) and potential therapeutics. (A), (1) Sterile insults cause primary tissue damage. (2) The damaged tissue releases various pro-inflammatory and pro-coagulative mediators, such as DAMPs and EVs. (3) Some mediators may not be cleared in the local damaged tissue and are released into the blood and circulated into remote organs. (4) These mediators will induce microthrombosis and local inflammation in the remote tissues, causing microinjuries. (5) The microinjured tissue subsequently releases de novo DAMPs and EVs, aggravating local tissue damages. Release of DAMPs and EVs and microinjuries in the remote tissues develops a vicious cycle and induces SOF. (B) Inhibition of inflammation and thrombosis using pattern recognition receptor (PRR) antagonists, PRR signaling inhibitor, DAMP inhibitor, EV biosynthesis inhibitors, and nucleic acid-binding cationic polymer (NABP) scavengers, thereby ameliorating and preventing SOF after tissue injury.