Hypoxia-inducible factor (HIF1α) gene expression in human shock states

Introduction: Hypoxia-inducible factor-1 (HIF1) controls the expression of genes involved in the cellular response to hypoxia. No information is available on its expression in critically ill patients. Thus, we designed the first clinical study in order to evaluate the role of HIF1 alpha as a prognosis marker in patients suffering from shock. Methods: Fifty consecutive adult patients with shock and 11 healthy volunteers were prospectively enrolled in the study. RNA was extracted from whole blood samples and expression of HIF1 alpha was assessed over the first four hours of shock. The primary objective was to assess HIF1 alpha as a prognostic marker in shock. Secondary objectives were to evaluate the role of HIF1 alpha as a diagnostic and follow-up marker. Patient survival was evaluated at day 28. Results: The causes of shock were sepsis (78%), hemorrhage (18%), and cardiac dysfunction (4%). HIF1 alpha expression was significantly higher in the shock patients than in the healthy volunteers (121 (range: 72-168) versus 48 (range: 38-54) normalized copies, P <0.01), whatever the measured isoforms. It was similar in non-survivors and survivors (108 (range 84-183) versus 121(range 72-185) normalized copies, P = 0.92), and did not significantly change within the study period. Conclusions: The present study is the first to demonstrate an increased expression of HIF1 alpha in patients with shock. Further studies are needed to clarify the potential association with outcome. Our findings reinforce the value of monitoring plasma lactate levels to guide the treatment of shock.