Mihir R Atreya, Natalie Z Cvijanovich, Julie C Fitzgerald, Scott L Weiss, Michael T Bigham, Parag N Jain, Adam J Schwarz, Riad Lutfi, Jeffrey Nowak, Geoffrey L Allen, Neal J Thomas, Jocelyn R Grunwell, Torrey Baines, Michael Quasney, Bereketeab Haileselassie, Matthew N Alder, Patrick Lahni, Scarlett Ripberger, Adesuwa Ekunwe, Kyle R Campbell, Keith R Walley, Stephen W Standage
BACKGROUND: Sepsis is associated with significant mortality. Yet, there are no efficacious therapies beyond antibiotics. PCSK9 loss-of-function (LOF) and inhibition, through enhanced low-density lipoprotein receptor (LDLR) mediated endotoxin clearance, holds promise as a potential therapeutic approach among adults. In contrast, we have previously demonstrated higher mortality in the juvenile host. Given the potential pleiotropic effects of PCSK9 on the endothelium, beyond canonical effects on serum lipoproteins, both of which may influence sepsis outcomes, we sought to test the influence of PCSK9 LOF genotype on endothelial dysfunction...
June 26, 2023: Critical Care: the Official Journal of the Critical Care Forum