Serpins in Angiogenesis

  • Czeslaw S. Cierniewski
  • Joanna BoncelaEmail author


Serpins (serine proteinase inhibitors) are the largest superfamily of protease inhibitors. The serpins are structurally similar but functionally diverse proteins that fold into a conserved structure and employ a unique suicide substrate-like inhibitory mechanism. Most of them act as classical protease inhibitors, but there are also serpins that inhibit other types of proteinases, e.g., caspases, or have different, noninhibitory functions, e.g., hormone transport. Serpins are involved in regulation of numerous biological pathways that initiate inflammation, coagulation, fibrinolysis, complement activation responses, apoptosis, extracellular matrix composition, and angiogenesis. The following serpins have been identified as potential regulators of angiogenesis: plasminogen activator inhibitor type 1 (PAI-1), kallistatin, protein C inhibitor, angiotensinogen, maspin, antithrombin, nexin-1, and pigment epithelial-derived factor. They exert mainly antiangiogenic activity, by inhibition of proteolytic processes in which serine proteases and matrix metalloproteinases (MMPs) are key players. Among them, PAI-1 appears to be the most controversial serpin in angiogenesis; it may act both as a pro- and antiangiogenic factor, depending upon the type of cells and existing conditions. Taken together, serpins remarkably contribute to vessels formation process; they are able to affect more than one of the angiogenic steps and their activity extend beyond the inhibition of target proteinases.


Serine protease inhibitors Plasminogen activator inhibitor type 1 Extracellular matrix Endothelial cells migration Plasmin-dependent proteolysis 



This work was supported by Projects DEC-2011/01/B/NZ3/00194 (J.B.) and DEC-2011/02/A/NZ3/00068 (C.S.C.).


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Copyright information

© Springer-Verlag Wien 2013

Authors and Affiliations

  1. 1.Institute of Medical Biology, Polish Academy of SciencesŁódźPoland
  2. 2.Department of Molecular and Medical BiophysicsMedical University of ŁódźŁódźPoland

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