PAI-1 as a critical factor in the resolution of sepsis and acute kidney injury in old age

• DOI: 10.3389/fcell.2023.1330433
• Publication Date: 2024-01-18T04:31:21Z
• Authors: Maria E. C. Bruno; Sujata Mukherjee; Jamie L. Sturgill; Virgilius Cornea; Peng Yeh; Gregory S. Hawk; Hiroshi Saito; Marlene E. Starr
• Keywords: Plasminogen activator inhibitor-1

Elevated plasma levels of plasminogen activator inhibitor type 1 (PAI-1) are documented in patients with sepsis and positively correlate disease severity mortality. Our prior work demonstrated that PAI-1 is associated acute kidney injury (AKI) septic mice. The objective this study was to determine if causally related AKI worse outcomes using a clinically-relevant age-appropriate murine model sepsis. Sepsis induced by cecal slurry (CS)-injection wild-type (WT, C57BL/6) knockout (KO) mice at young (5–9 months) old (18–22 age. Survival monitored for least 10 days or were euthanized tissue collection 24 48 h post-insult. Contrary our expectation, KO age significantly more sensitive CS-induced compared WT (24% vs. 65% survival, p = 0.0037). In comparison, loss had negligible effects on survival (86% 88% 0.8106) highlighting the importance as biological variable. Injury most apparent pathological consequence occurred earlier aged Coagulation markers unaffected PAI-1, suggesting thrombosis-independent mechanisms PAI-1-mediated protection. summary, although high clinically outcomes, rendered susceptible death These results implicate critical factor resolution