Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis
Epidemiological studies confirm the high risk of ischemic events in multiple sclerosis (MS) that are associated with increased pro-thrombotic activity of blood platelets. The most potent physiological platelet agonist is thrombin, which activates platelets via cleavage of specific protease-activated...
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MDPI AG
2020-10-01
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| Series: | International Journal of Molecular Sciences |
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| Online Access: | https://www.mdpi.com/1422-0067/21/20/7722 |
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| author | Angela Dziedzic Elzbieta Miller Michal Bijak Lukasz Przyslo Joanna Saluk-Bijak |
| author_facet | Angela Dziedzic Elzbieta Miller Michal Bijak Lukasz Przyslo Joanna Saluk-Bijak |
| author_sort | Angela Dziedzic |
| collection | DOAJ |
| description | Epidemiological studies confirm the high risk of ischemic events in multiple sclerosis (MS) that are associated with increased pro-thrombotic activity of blood platelets. The most potent physiological platelet agonist is thrombin, which activates platelets via cleavage of specific protease-activated receptors (PARs). Our current study is aimed to determine the potential genetics and proteomic abnormalities of PAR1 in both platelets and megakaryocytes, which may have thromboembolic consequences in the course of MS. The obtained results were correlated with the expression level of platelet and megakaryocyte transcripts for <i>APOA1</i> and <i>A2M</i> genes encoding atherosclerosis biomarkers: apolipoprotein A1 (ApoA1) and α-2-macroglobulin (α2M), respectively. Moreover, PAR1 functionality in MS platelets was assessed by flow cytometry, determining the level of platelet–platelet and platelet–leukocyte aggregates, platelet microparticles and surface expression of P-selectin. As a PAR1 agonist, the synthetic TRAP-6 peptide was used, which made it possible to achieve platelet activation in whole blood without triggering clotting. Comparative analyses showed an elevated level of platelet activation markers in the blood of MS patients compared to controls. The mRNA expression of gene coding α2M was upregulated, whilst ApoA1 was down-regulated, both in platelets and megakaryocytes from MS patients. Furthermore, we observed an increase in both mRNA expression and surface density of PAR1 in platelets and megakaryocytes in MS compared to controls. Both the level of platelet activation markers and PAR1 expression showed a high correlation with the expression of transcripts for <i>APOA1</i> and <i>A2M</i> genes. |
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| language | English |
| last_indexed | 2024-03-10T15:30:40Z |
| publishDate | 2020-10-01 |
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| series | International Journal of Molecular Sciences |
| spelling | doaj.art-88f31e41bc944849b1ed73b871b6f6a72023-11-20T17:38:17ZengMDPI AGInternational Journal of Molecular Sciences1661-65961422-00672020-10-012120772210.3390/ijms21207722Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple SclerosisAngela Dziedzic0Elzbieta Miller1Michal Bijak2Lukasz Przyslo3Joanna Saluk-Bijak4Department of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, PolandDepartment of Neurological Rehabilitation, Medical University of Lodz, Milionowa 14, 93-113 Lodz, PolandBiohazard Prevention Centre, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, PolandDepartment of Developmental Neurology and Epileptology, Research Institute of Polish Mother’s Memorial Hospital, Rzgowska 281/289, 93-338 Lodz, PolandDepartment of General Biochemistry, Faculty of Biology and Environmental Protection, University of Lodz, Pomorska 141/143, 90-236 Lodz, PolandEpidemiological studies confirm the high risk of ischemic events in multiple sclerosis (MS) that are associated with increased pro-thrombotic activity of blood platelets. The most potent physiological platelet agonist is thrombin, which activates platelets via cleavage of specific protease-activated receptors (PARs). Our current study is aimed to determine the potential genetics and proteomic abnormalities of PAR1 in both platelets and megakaryocytes, which may have thromboembolic consequences in the course of MS. The obtained results were correlated with the expression level of platelet and megakaryocyte transcripts for <i>APOA1</i> and <i>A2M</i> genes encoding atherosclerosis biomarkers: apolipoprotein A1 (ApoA1) and α-2-macroglobulin (α2M), respectively. Moreover, PAR1 functionality in MS platelets was assessed by flow cytometry, determining the level of platelet–platelet and platelet–leukocyte aggregates, platelet microparticles and surface expression of P-selectin. As a PAR1 agonist, the synthetic TRAP-6 peptide was used, which made it possible to achieve platelet activation in whole blood without triggering clotting. Comparative analyses showed an elevated level of platelet activation markers in the blood of MS patients compared to controls. The mRNA expression of gene coding α2M was upregulated, whilst ApoA1 was down-regulated, both in platelets and megakaryocytes from MS patients. Furthermore, we observed an increase in both mRNA expression and surface density of PAR1 in platelets and megakaryocytes in MS compared to controls. Both the level of platelet activation markers and PAR1 expression showed a high correlation with the expression of transcripts for <i>APOA1</i> and <i>A2M</i> genes.https://www.mdpi.com/1422-0067/21/20/7722thromboembolic consequences in multiple sclerosisprotease-activated receptorsblood plateletsmegakaryocytes |
| spellingShingle | Angela Dziedzic Elzbieta Miller Michal Bijak Lukasz Przyslo Joanna Saluk-Bijak Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis International Journal of Molecular Sciences thromboembolic consequences in multiple sclerosis protease-activated receptors blood platelets megakaryocytes |
| title | Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis |
| title_full | Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis |
| title_fullStr | Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis |
| title_full_unstemmed | Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis |
| title_short | Increased Pro-Thrombotic Platelet Activity Associated with Thrombin/PAR1-Dependent Pathway Disorder in Patients with Secondary Progressive Multiple Sclerosis |
| title_sort | increased pro thrombotic platelet activity associated with thrombin par1 dependent pathway disorder in patients with secondary progressive multiple sclerosis |
| topic | thromboembolic consequences in multiple sclerosis protease-activated receptors blood platelets megakaryocytes |
| url | https://www.mdpi.com/1422-0067/21/20/7722 |
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