Recombinant plasminogen activator inhibitor type 1: a review of structural, functional, and biological aspects.
Plasminogen activator inhibitor type 1 (PAI-1), a member of the serpin family of serine protease inhibitors, inhibits both tissue-type plasminogen activator (t-PA) and urokinase type plasminogen activator (u-PA). High PAI-1 levels are associated with an increased risk of thromboembolic disease while PAI-1 deficiency may represent an inherited autosomal recessive bleeding disorder. This review describes the biochemistry of PAI-1 including its purification, conversion between active and latent forms, and interaction with its target serine proteases and its protein cofactor, vitronectin. In addition, an overview of animal studies with PAI-1 is presented to examine its role in regulating fibrinolysis in vivo. For this review, particular emphasis is placed on studies with a recombinant form of bacterially expressed PAI-1 (rPAI-1), which shares many features in common with the active form of native PAI-1.
Reilly
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Du Pont Merck Pharmaceutical Company, Experimental Station, Wilmington, DE 19880-0400.
Mousa
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Seetharam
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Racanelli
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D000818:Animals; D005342:Fibrinolysis; D015870:Gene Expression; D006487:Hemostasis; D006801:Humans; D017395:Plasminogen Activator Inhibitor 1 / Q000737:chemistry / Q000235:genetics / Q000302:isolation & purification / Q000493:pharmacokinetics / Q000494:pharmacology / Q000502:physiology; D011994:Recombinant Proteins
D017395:Plasminogen Activator Inhibitor 1; D011994:Recombinant Proteins