Plasminogen Activator Inhibitors (PAIs) are crucial components of the fibrinolytic system, which regulates blood clot dissolution. The most studied PAIs are PAI-1 and PAI-2. These proteins inhibit tissue plasminogen activator (tPA) and urokinase-type plasminogen activator (uPA), thereby controlling the conversion of plasminogen to plasmin and modulating fibrinolysis.

Technical Details

Structure:

• PAI-1: A serpin (serine protease inhibitor) with a unique ability to convert between active and latent forms. It forms a complex with tPA or uPA to inhibit their activity.
• PAI-2: A non-glycosylated protein that also belongs to the serpin family but is less stable and primarily functions intracellularly.

Production:

• PAI recombinant proteins are produced using recombinant DNA technology in systems such as E. coli, yeast, insect, or mammalian cells.
• Recombinant production ensures high purity, activity, and structural integrity of the proteins, suitable for biochemical and functional studies.

Applications:

• Thrombosis and Hemostasis Research:
  • Studying the role of PAIs in regulating fibrinolysis and their contribution to thrombotic disorders.
  • Understanding the balance between coagulation and fibrinolysis in various physiological and pathological conditions.
• Cancer Research:
  • PAIs are implicated in cancer progression, metastasis, and angiogenesis.
  • Investigating the expression and function of PAIs in tumor biology and their potential as therapeutic targets.
• Cardiovascular Disease:
  • Researching the involvement of PAIs in cardiovascular diseases such as myocardial infarction, stroke, and atherosclerosis.
  • Developing diagnostic and therapeutic strategies based on PAI levels and activity.
• Drug Development:
  • Screening and characterization of small molecule inhibitors, peptides, and monoclonal antibodies that modulate PAI activity.
  • Developing therapeutic agents targeting PAI-1 for thrombolytic therapy.

Analytical Methods:

• Enzyme-Linked Immunosorbent Assay (ELISA): For quantification of PAI levels in biological samples.
• Western Blotting: For detection and analysis of PAI proteins and their complexes.
• Surface Plasmon Resonance (SPR): To study the interaction kinetics between PAIs and their targets (tPA and uPA).
• Activity Assays: To measure the inhibitory activity of recombinant PAIs on plasminogen activators.