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Platelets synthesize large amounts of active plasminogen activator inhibitor 1

Brogren, H; Karlsson, L; Andersson, M; Wang, Lingwei LU ; Erlinge, David LU and Jern, S (2004) In Blood 104(13). p.3943-3948
Abstract
Previous studies have suggested that plasminogen activator inhibitor 1 (PAI-1) released from platelets convey resistance of platelet-rich blood clots to thrombolysis. However, the majority of PAI-1 in platelets is inactive and therefore its role in clot stabilization is unclear. Because platelets retain mRNA and capacity for synthesis of some proteins, we investigated if platelets can de novo synthesize PAI-1 with an active configuration. PAI-1 mRNA was quantified with real-time polymerase chain reaction and considerable amounts of PAW mRNA were detected in all platelet samples. Over 24 hours, the amount of PAI-1 protein as determined by an enzyme-linked immunosorbent assay increased by 25% (P = .001). Metabolic radiolabeling with... (More)
Previous studies have suggested that plasminogen activator inhibitor 1 (PAI-1) released from platelets convey resistance of platelet-rich blood clots to thrombolysis. However, the majority of PAI-1 in platelets is inactive and therefore its role in clot stabilization is unclear. Because platelets retain mRNA and capacity for synthesis of some proteins, we investigated if platelets can de novo synthesize PAI-1 with an active configuration. PAI-1 mRNA was quantified with real-time polymerase chain reaction and considerable amounts of PAW mRNA were detected in all platelet samples. Over 24 hours, the amount of PAI-1 protein as determined by an enzyme-linked immunosorbent assay increased by 25% (P = .001). Metabolic radiolabeling with S-35-methionine followed by immunoprecipitation confirmed an ongoing PAI-1 synthesis, which could be further stimulated by thrombin and inhibited by puromycin. The activity of the newly formed PAI-1 was investigated by incubating platelets in the presence of tissue-type plasminogen activator (tPA). This functional assay showed that the majority of the new protein was in an active configuration and could complex-bind tPA. Thus, there is a continuous production of large amounts of active PAI-1 in platelets, which could be a mechanism by which platelets contribute to stabilization of blood clots. (Less)
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author
organization
publishing date
type
Contribution to journal
publication status
published
subject
in
Blood
volume
104
issue
13
pages
3943 - 3948
publisher
American Society of Hematology
external identifiers
  • pmid:15315974
  • wos:000225601000025
  • scopus:10244249152
ISSN
1528-0020
DOI
10.1182/blood-2004-04-1439
language
English
LU publication?
yes
id
a518147f-f2ba-4827-9337-fe529c71e4a5 (old id 259364)
date added to LUP
2007-10-17 12:48:39
date last changed
2017-12-03 03:21:38
@article{a518147f-f2ba-4827-9337-fe529c71e4a5,
  abstract     = {Previous studies have suggested that plasminogen activator inhibitor 1 (PAI-1) released from platelets convey resistance of platelet-rich blood clots to thrombolysis. However, the majority of PAI-1 in platelets is inactive and therefore its role in clot stabilization is unclear. Because platelets retain mRNA and capacity for synthesis of some proteins, we investigated if platelets can de novo synthesize PAI-1 with an active configuration. PAI-1 mRNA was quantified with real-time polymerase chain reaction and considerable amounts of PAW mRNA were detected in all platelet samples. Over 24 hours, the amount of PAI-1 protein as determined by an enzyme-linked immunosorbent assay increased by 25% (P = .001). Metabolic radiolabeling with S-35-methionine followed by immunoprecipitation confirmed an ongoing PAI-1 synthesis, which could be further stimulated by thrombin and inhibited by puromycin. The activity of the newly formed PAI-1 was investigated by incubating platelets in the presence of tissue-type plasminogen activator (tPA). This functional assay showed that the majority of the new protein was in an active configuration and could complex-bind tPA. Thus, there is a continuous production of large amounts of active PAI-1 in platelets, which could be a mechanism by which platelets contribute to stabilization of blood clots.},
  author       = {Brogren, H and Karlsson, L and Andersson, M and Wang, Lingwei and Erlinge, David and Jern, S},
  issn         = {1528-0020},
  language     = {eng},
  number       = {13},
  pages        = {3943--3948},
  publisher    = {American Society of Hematology},
  series       = {Blood},
  title        = {Platelets synthesize large amounts of active plasminogen activator inhibitor 1},
  url          = {http://dx.doi.org/10.1182/blood-2004-04-1439},
  volume       = {104},
  year         = {2004},
}