急性肺障害における血管内皮前駆細胞の動態解析:自家移植による再生治療の試み

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Objective : Impaired fibrinolysis is associated with a higher incidence of both multiple organ dysfunction and mortality in the intensive care unit(ICU). Plasminogen activator inhibitor(PAI)-1 is the chief inhibitor of fibrinolysis. We investigated the influence of the 4G/5G polymorphism(rs1799768) of the PAI-1 gene on the plasma PAI-1 level and the outcome of critically ill patients. Methods : In 41 consecutive patients admitted to the ICU, PAI-1 gene polymorphism was assessed, plasma PAI-1 and arterial lactate concentrations were measured and clinical severity scores were recorded. Results : Homozygotes for the 4G allele had higher plasma levels of PAI-1 antigen. The mean 8 SD PAI-1 antigen level was 193.318 167.93 ng/ml for the 4G/4G genotype, 100.67 8 114.16 ng/ml for the 4G/5G genotype and 0.43 8 0.53 ng/ml for the 5G/5G genotype. There was a significant correlation between plasma PAI-1 and arterial lactate concentrations, as well as between PAI-1 and severity scores. The mortality rate was 63, 33 and 0% for patients with the 4G/4G, 4G/5G and 5G/5G genotypes, respectively. Conclusions : These results demonstrate that the 4G/5G polymorphism of the PAI-1 gene affects the plasma PAI-1 concentration, which could impair fibrinolysis and cause organ failure, and thus the presence of the 4G allele increases the risk of death.