T. Fujita et al., Paradoxical rescue from ischemic lung injury by inhaled carbon monoxide driven by derepression of fibrinolysis, NAT MED, 7(5), 2001, pp. 598-604
Citations number
45
Categorie Soggetti
Research/Laboratory Medicine & Medical Tecnology","Medical Research General Topics
Carbon monoxide (CO) can arrest cellular respiration, but paradoxically, it
is synthesized endogenously by heme oxygenase type 1 (Ho-1) in response to
ischemic stress. Ho-1-deficient (Hmox1(-/-)) mice exhibited lethal ischemi
c lung injury, but were rescued from death by inhaled CO. CO drove ischemic
protection by activating soluble guanylate cyclase and thereby suppressed
hypoxic induction of the gene encoding plasminogen activator inhibitor-1 (P
AI-1) in mononuclear phagocytes, which reduced accrual of microvascular fib
rin. GO-mediated ischemic protection observed in wild-type mice was lost in
mice null for the gene encoding PAI-1 (Serpine1). These data establish a f
undamental link between CO and prevention of ischemic injury based on the a
bility of CO to derepress the fibrinolytic axis. These data also point to a
potential therapeutic use for inhaled CO.