Dissecting the role of PCSK9 in sepsis
Severe sepsis strikes young and old alike with an increasing incidence of >75,000 per year in Canada at a cost of $40,000 per patient. In 40% sepsis is complicated by low blood pressure and organ failure with a mortality rate of 30-60%. The number of deaths due to severe sepsis and septic shock is greater than the number of deaths due to acute myocardial infarction. The process that links infection to organ failure and death is triggered by bacterial toxins, including lipopolysaccharide, lipoteichoic acid, and phospholipomannan. Pathogen toxins are cleared from the blood by the liver. We have recently discovered that inhibition of Proprotein Convertase Subtilisin/Kexin type-9 (PCSK9) improves survival in septic shock, possibly by altering clearance of pathogen toxins. This research will discover how best to neutralize PCSK9.