Plasminogen modulates formation and release of platelet angiogenic regulators
Platelets store, produce and release a variety of angiogenesis regulators, which can contribute to both normal tissue repair and angiopathy-associated pathologies. Plasminogen has been earlier shown to regulate some platelet functions, but if it is able to modulate angiogenic capacities of platelets...
| Main Authors: | , , |
|---|---|
| Format: | Article |
| Language: | English |
| Published: |
National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry
2020-02-01
|
| Series: | The Ukrainian Biochemical Journal |
| Subjects: | |
| Online Access: | http://ukrbiochemjournal.org/wp-content/uploads/2020/02/Tykhomyrov_1_20.pdf |
| _version_ | 1797427834051887104 |
|---|---|
| author | A. A. Tykhomyrov D. D. Zhernosekov T. V. Grinenko |
| author_facet | A. A. Tykhomyrov D. D. Zhernosekov T. V. Grinenko |
| author_sort | A. A. Tykhomyrov |
| collection | DOAJ |
| description | Platelets store, produce and release a variety of angiogenesis regulators, which can contribute to both normal tissue repair and angiopathy-associated pathologies. Plasminogen has been earlier shown to regulate some platelet functions, but if it is able to modulate angiogenic capacities of platelets is still poorly studied. Thus, the aim of the present study was to evaluate the effects of different plasminogen forms on the formation and secretion of angiogenic protein regulators by platelets. Human washed platelets were obtained by gel-filtration on Sepharose-2B. The levels of P-selectin (CD-62P) exposed on the plasma membrane of untreated and activated platelets was monitored by flow cytometry. Secretion of platelet-derived vascular endothelial growth factor (VEGF) as well as plasminogen fragmentation and angiostatin formation by intact platelets and platelet plasma membranes were analyzed by immunoblotting. It was shown that thrombin or collagen exposure resulted in enhanced P-selectin surface expression by platelets, while Lys-form of plasminogen reduced agonist-induced platelet secretion. Lys-plasminogen, but not Glu-form, inhibited agonist-induced VEGF release from platelets. Activation of platelets significantly accelerated plasminogen cleavage and angiostatin formation. Anti-actin antibodies inhibited plasminogen fragmentation during incubation with platelet plasma membranes indicating surface-exposed actin participation in plasminogen conversion to angiostatins. The present study uncovers a novel function of plasminogen to limit angiogenic potential of platelets via angiostatin formation and inhibition of VEGF secretion. |
| first_indexed | 2024-03-09T08:50:27Z |
| format | Article |
| id | doaj.art-fd349aa18c6e4f93a9e5b409b2a7f720 |
| institution | Directory Open Access Journal |
| issn | 2409-4943 2413-5003 |
| language | English |
| last_indexed | 2024-03-09T08:50:27Z |
| publishDate | 2020-02-01 |
| publisher | National Academy of Sciences of Ukraine, Palladin Institute of Biochemistry |
| record_format | Article |
| series | The Ukrainian Biochemical Journal |
| spelling | doaj.art-fd349aa18c6e4f93a9e5b409b2a7f7202023-12-02T14:35:56ZengNational Academy of Sciences of Ukraine, Palladin Institute of BiochemistryThe Ukrainian Biochemical Journal2409-49432413-50032020-02-01921314010.15407/ubj92.01.031Plasminogen modulates formation and release of platelet angiogenic regulatorsA. A. Tykhomyrov0D. D. Zhernosekov1T. V. Grinenko2Palladin Institute of Biochemistry, National Academy of Sciences of Ukraine, KyivPalladin Institute of Biochemistry, National Academy of Sciences of Ukraine, KyivPalladin Institute of Biochemistry, National Academy of Sciences of Ukraine, KyivPlatelets store, produce and release a variety of angiogenesis regulators, which can contribute to both normal tissue repair and angiopathy-associated pathologies. Plasminogen has been earlier shown to regulate some platelet functions, but if it is able to modulate angiogenic capacities of platelets is still poorly studied. Thus, the aim of the present study was to evaluate the effects of different plasminogen forms on the formation and secretion of angiogenic protein regulators by platelets. Human washed platelets were obtained by gel-filtration on Sepharose-2B. The levels of P-selectin (CD-62P) exposed on the plasma membrane of untreated and activated platelets was monitored by flow cytometry. Secretion of platelet-derived vascular endothelial growth factor (VEGF) as well as plasminogen fragmentation and angiostatin formation by intact platelets and platelet plasma membranes were analyzed by immunoblotting. It was shown that thrombin or collagen exposure resulted in enhanced P-selectin surface expression by platelets, while Lys-form of plasminogen reduced agonist-induced platelet secretion. Lys-plasminogen, but not Glu-form, inhibited agonist-induced VEGF release from platelets. Activation of platelets significantly accelerated plasminogen cleavage and angiostatin formation. Anti-actin antibodies inhibited plasminogen fragmentation during incubation with platelet plasma membranes indicating surface-exposed actin participation in plasminogen conversion to angiostatins. The present study uncovers a novel function of plasminogen to limit angiogenic potential of platelets via angiostatin formation and inhibition of VEGF secretion.http://ukrbiochemjournal.org/wp-content/uploads/2020/02/Tykhomyrov_1_20.pdfangiogenesisangiostatinsplasminogenplateletsvascular endothelial growth factor (vegf) |
| spellingShingle | A. A. Tykhomyrov D. D. Zhernosekov T. V. Grinenko Plasminogen modulates formation and release of platelet angiogenic regulators The Ukrainian Biochemical Journal angiogenesis angiostatins plasminogen platelets vascular endothelial growth factor (vegf) |
| title | Plasminogen modulates formation and release of platelet angiogenic regulators |
| title_full | Plasminogen modulates formation and release of platelet angiogenic regulators |
| title_fullStr | Plasminogen modulates formation and release of platelet angiogenic regulators |
| title_full_unstemmed | Plasminogen modulates formation and release of platelet angiogenic regulators |
| title_short | Plasminogen modulates formation and release of platelet angiogenic regulators |
| title_sort | plasminogen modulates formation and release of platelet angiogenic regulators |
| topic | angiogenesis angiostatins plasminogen platelets vascular endothelial growth factor (vegf) |
| url | http://ukrbiochemjournal.org/wp-content/uploads/2020/02/Tykhomyrov_1_20.pdf |
| work_keys_str_mv | AT aatykhomyrov plasminogenmodulatesformationandreleaseofplateletangiogenicregulators AT ddzhernosekov plasminogenmodulatesformationandreleaseofplateletangiogenicregulators AT tvgrinenko plasminogenmodulatesformationandreleaseofplateletangiogenicregulators |