Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA
Background: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and...
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| Format: | Article |
| Language: | English |
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MDPI AG
2024-02-01
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| Series: | Cancers |
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| Online Access: | https://www.mdpi.com/2072-6694/16/5/928 |
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| author | Matti Ullah Shahsoltan Mirshahi Azadeh Valinattaj Omran Iman Aldybiat Sullyvan Crepaux Jeannette Soria Geneviève Contant Marc Pocard Massoud Mirshahi |
| author_facet | Matti Ullah Shahsoltan Mirshahi Azadeh Valinattaj Omran Iman Aldybiat Sullyvan Crepaux Jeannette Soria Geneviève Contant Marc Pocard Massoud Mirshahi |
| author_sort | Matti Ullah |
| collection | DOAJ |
| description | Background: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Methods: Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Results: Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots’ permeability, but also makes them more prone to degradation. Conclusions: Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis. |
| first_indexed | 2024-04-25T00:33:50Z |
| format | Article |
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| institution | Directory Open Access Journal |
| issn | 2072-6694 |
| language | English |
| last_indexed | 2024-04-25T00:33:50Z |
| publishDate | 2024-02-01 |
| publisher | MDPI AG |
| record_format | Article |
| series | Cancers |
| spelling | doaj.art-e865ce13c7464b09a10b162f226caf4d2024-03-12T16:40:52ZengMDPI AGCancers2072-66942024-02-0116592810.3390/cancers16050928Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNAMatti Ullah0Shahsoltan Mirshahi1Azadeh Valinattaj Omran2Iman Aldybiat3Sullyvan Crepaux4Jeannette Soria5Geneviève Contant6Marc Pocard7Massoud Mirshahi8CAP-Paris Tech., INSERM U1275, Université Paris Cité, Hôpital Lariboisière, 75010 Paris, FranceProspective Research, Diagnostica Stago, 92230 Gennevilliers, FranceCAP-Paris Tech., INSERM U1275, Université Paris Cité, Hôpital Lariboisière, 75010 Paris, FranceCAP-Paris Tech., INSERM U1275, Université Paris Cité, Hôpital Lariboisière, 75010 Paris, FranceCAP-Paris Tech., INSERM U1275, Université Paris Cité, Hôpital Lariboisière, 75010 Paris, FranceCAP-Paris Tech., INSERM U1275, Université Paris Cité, Hôpital Lariboisière, 75010 Paris, FranceProspective Research, Diagnostica Stago, 92230 Gennevilliers, FranceCAP-Paris Tech., INSERM U1275, Université Paris Cité, Hôpital Lariboisière, 75010 Paris, FranceCAP-Paris Tech., INSERM U1275, Université Paris Cité, Hôpital Lariboisière, 75010 Paris, FranceBackground: Blood viscoelasticity and plasma protein levels can play an important role in the diagnosis and prognosis of cancer. However, the role of histones and DNA in modulating blood clot properties remains to be investigated. This study investigates the differences in blood viscoelasticity and plasma protein levels among cancer patients, individuals with other diseases, and healthy individuals. Methods: Blood samples were collected from 101 participants, including 45 cancer patients, 22 healthy individuals, and 34 individuals with other diseases. Rheological properties of clots formed in vitro by reconstituted elements of fibrinogen or plasma were analyzed with an Anton Paar Rheometer, USA. Plasma protein levels of D-dimer, TPA, EPCR, fibrinogen, and histone H3 were measured through ELISA. Blood clots were formed with or without DNA and histones (H3) by adding thrombin and calcium to plasma samples, and were evaluated for viscoelasticity, permeability, and degradation. Results: Cancer patients show higher blood viscoelasticity and plasma D-dimer levels compared to healthy individuals and individuals with other diseases. Our in vitro analysis showed that the addition of histone to the plasma results in a significant decrease in viscoelasticity and mean fiber thickness of the clot formed thereafter. In parallel studies, using plasma from patients, DNA and histones were detected in fibrin clots and were associated with less degradation by t-PA. Moreover, our results show that the presence of DNA and histones not only increases clots’ permeability, but also makes them more prone to degradation. Conclusions: Plasma histones and DNA affect the structure of the clot formed and induce defective fibrinolysis. Moreover, the increased viscoelastic properties of plasma from cancer patients can be used as potential biomarkers in cancer prognosis.https://www.mdpi.com/2072-6694/16/5/928blood viscoelasticityplasma histonescancer rheologyclot degradationcancer thrombosis |
| spellingShingle | Matti Ullah Shahsoltan Mirshahi Azadeh Valinattaj Omran Iman Aldybiat Sullyvan Crepaux Jeannette Soria Geneviève Contant Marc Pocard Massoud Mirshahi Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA Cancers blood viscoelasticity plasma histones cancer rheology clot degradation cancer thrombosis |
| title | Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA |
| title_full | Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA |
| title_fullStr | Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA |
| title_full_unstemmed | Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA |
| title_short | Blood Clot Dynamics and Fibrinolysis Impairment in Cancer: The Role of Plasma Histones and DNA |
| title_sort | blood clot dynamics and fibrinolysis impairment in cancer the role of plasma histones and dna |
| topic | blood viscoelasticity plasma histones cancer rheology clot degradation cancer thrombosis |
| url | https://www.mdpi.com/2072-6694/16/5/928 |
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