Posted by Leanne Kodsmann on
Plasminogen Activator Inhibitor 1 (PAI-1) is a key component of fibrinolysis, the process by which the body is able to break apart a cross-linked fibrin clot. As an inhibitor of both tPA and uPA, PAI-1 is the primary inhibitor among the plasminogen activators and plays an important role in allowing appropriate clotting to occur. PAI-1 also plays a role in different conditions and diseases.
What is PAI-1 and what does it do?
Plasminogen Activator Inhibitor 1, commonly referred to as PAI-1 and sometimes called Endothelial Plasminogen Activator Inhibitor or SERPINE1, is a serine protease inhibitor (serpin) whose primary function is inhibiting Tissue Plasminogen Activator (tPA) and Urokinase (uPA).
Both tPA and uPA are enzymes that cleave plasminogen into plasmin as part of fibrinolysis, which is the body's way of breaking apart blood clots. PAI-1 is the primary inhibitor among the plasminogen activators and therefore plays an important role in allowing appropriate clotting to occur within the body.
In addition to its role as a serine protease inhibitor, PAI-1 also acts as a regulator of cell migration and influences cellular and replicative senescence. PAI-1 inhibits matrix metalloproteinase activity, which impacts the invasion of malignant cells through a layer of extracellular matrix produced by epithelial cells called the basal lamina. Recent research also points to PAI-1 as being a factor of predisposition in major depressive disorder and antidepressant drug resistance.
PAI-1 is produced primarily by the endothelium, but is also produced by adipose tissue and other tissue types. It can be found in plasma, platelets, and tumor cells like hepatoma and fibrosarcoma cells.
What is PAI-1 deficiency and how is it involved in disease?
A congenital, genetic PAI-1 deficiency is typically caused by mutations to the SERPINE1 gene. A rare PAI-1D mutation is documented within the Old Order Amish community, which results in a shortened and ineffective PAI-1 protein.
An individual with a homozygous PAI-1D mutation has unusually low levels of PAI-1, and will likely suffer incidents of hemorrhage (although usually not fatal), due to the increased breaking down of blood clots as a result of the PAI-1 deficiency. If the PAI-1 is not present and functioning to inhibit tPA and uPA, it is more difficult for stable blood clots to develop within the body.
In direct contrast, an individual with a heterozygous mutation will not demonstrate impaired coagulation and fibrinolysis. Furthermore, heterozygous individuals seem to demonstrate additional biomarkers of interest, many of which indicate better health outcomes (as observed in populations with this known genetic occurrence, like the Old Order Amish). These biomarkers include longer leukocyte telomere length, a reduced fasting insulin level, lower occurrence of diabetes, and an increased overall life span.
Supporting PAI-1 Research
Innovative Research, Inc. has a wide range of PAI-1 related products from numerous species, including purified preparations, mutant versions, polyclonal and monoclonal antibodies, and ELISA Kits (both active and total).
We are also introducing a line of PAI-1 Knockout Mice, available as individual male and/or female mice as well as breeding pairs. These Research Models are fully licensed and maintained as live colonies with immediate availability. Contact us directly for more information about live Research Models.
Looking for a shortcut? We also offer a range of ready-to-use PAI-1 Mouse Knockout products. These are collected from mice with targeted disruption of SERPIN1, confirmed to be homozygous by PCR genotyping and Sanger sequencing. We have Mouse PAI-1 Knockout (genetically deficient) plasma available, as well as whole organs, lyophilized organs, and tissue lysates.