Title: IRE1 Deficiency in the Liver: A Novel Mechanism of Cardiac Inflammation in Sepsis
Monday, March 20, 2023


Juan Rodriguez Centeno

Abstract:  Sepsis is a leading cause of death in the intensive care unit, with current treatment options being limited to supportive care. The heart is particularly affected by the multiple organ dysfunction caused by sepsis, with cardiomyopathy playing a significant role in the severity and mortality of the condition. Studies have shown that the liver supports heart function through the secretion of lipids during sepsis, however, our understanding of how this inter-organ communication is regulated remains limited. Our preliminary data suggest that Inositol Requiring Enzyme 1 (IRE1) is downregulated during sepsis in the liver, leading to increased heart inflammation and mortality in septic mice. In addition, we found that IRE1 induces the production of Lysophosphatidylcholine (LPC) 18:0, which positively correlates with sepsis survival in humans and was previously shown to have beneficial effects in septic mice. Therefore, we hypothesize that sepsis suppresses IRE1 in the liver, resulting in defective lipid signaling that augments cardiac inflammation. To test this hypothesis, we will use a multidisciplinary approach to investigate the causes of this defective signaling and the molecular mechanisms of the protective effects of IRE1-mediated lipid signaling on septic cardiac inflammation. The findings from this study have the potential to provide new therapeutic targets for managing sepsis in the clinic. The AHA grant will cover two years of Juan’s salary and support for travel, equipment in the amount of $65,106.

Congratulations Juan!