Septic shock with multiple organ failure is the leading cause of death in non-coronary intensive care units and remains a major health problem in the US. Despite improvements in overall ICU care, efforts to discover targeted therapies for sepsis have been disappointing to date. Endothelial cell (EC) dysfunction, manifested by increases in vascular permeability, is an important hallmark of septic shock and plays a critical role in the pathogenesis of multi-organ failure. The long-term goal of our research is to identify novel treatment strategies to maintain endothelial barrier function in sepsis.
1. Endothelial progenitor cells (EPC)s are bone marrow-derived endothelial precursor cells, which play critical roles in endothelial regeneration and repair. Circulating EPCs recently have been associated with sepsis. Specifically, EPCs from humans with sepsis demonstrate alterations in function and EPC proliferation is inversely related to organ dysfunction when compared to EPCs from healthy controls. The overall objective for this project is to identify the mechanisms by which EPCs modulate endothelial barrier dysfunction in sepsis. We are interested in therapeutic potential of EPC exosomes containing miRNAs.
2. Pericytes (PC) maintain endothelial barrier function and represent a potential therapeutic target in sepsis. However, the processes that govern pericyte viability and their role in barrier function in sepsis have not yet been fully elucidated. The overall objective for this porject is to identify the determinants of pericyte viability in sepsis and the mechanisms by which pericytes maintain endothelial barrier function.