Project 171780

Sepsis is one of the main consequences of infectious diseases and occurs in 2-11% of all hospital or intensive care unit admissions. Mortality is 20-30% in sepsis and 40-80% in septic shock. Cardiac dysfunction is a common complication of septic shock. Lipopolysaccharide (LPS), the endotoxin of Gram-negative bacteria induces tumor necrosis factor-alpha (TNF-alpha), a pro-inflammatory cytokine. TNF-alpha is one of the main mediators responsible for cardiac dysfunction in sepsis. However, mechanisms leading to TNF-alpha production in the heart in sepsis are not fully understood. The goal of this proposal is to study the role of Rac1, a signaling molecule in the regulation of myocardial TNF-alpha expression and cardiac function during sepsis. The proposal will increase our understanding on mechanisms regulating TNF-alpha expression in sepsis, and may have therapeutic implications in the treatment of sepsis.