MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes
Abstract Background Diabetes mellitus is characterized by chronic vascular disorder and presents a main risk factor for cardiovascular mortality. In particular, hyperglycaemia and inflammatory cytokines induce vascular circulating tissue factor (TF) that promotes pro-thrombotic conditions in diabete...
| Main Authors: | , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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BMC
2018-02-01
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| Series: | Cardiovascular Diabetology |
| Subjects: | |
| Online Access: | http://link.springer.com/article/10.1186/s12933-018-0678-z |
| _version_ | 1818911274901176320 |
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| author | Marco Witkowski Termeh Tabaraie Daniel Steffens Julian Friebel Andrea Dörner Carsten Skurk Mario Witkowski Bernd Stratmann Diethelm Tschoepe Ulf Landmesser Ursula Rauch |
| author_facet | Marco Witkowski Termeh Tabaraie Daniel Steffens Julian Friebel Andrea Dörner Carsten Skurk Mario Witkowski Bernd Stratmann Diethelm Tschoepe Ulf Landmesser Ursula Rauch |
| author_sort | Marco Witkowski |
| collection | DOAJ |
| description | Abstract Background Diabetes mellitus is characterized by chronic vascular disorder and presents a main risk factor for cardiovascular mortality. In particular, hyperglycaemia and inflammatory cytokines induce vascular circulating tissue factor (TF) that promotes pro-thrombotic conditions in diabetes. It has recently become evident that alterations of the post-transcriptional regulation of TF via specific microRNA(miR)s, such as miR-126, contribute to the pathogenesis of diabetes and its complications. The endothelial miR-19a is involved in vascular homeostasis and atheroprotection. However, its role in diabetes-related thrombogenicity is unknown. Understanding miR-networks regulating procoagulability in diabetes may help to develop new treatment options preventing vascular complications. Methods and results Plasma of 44 patients with known diabetes was assessed for the expression of miR-19a, TF protein, TF activity, and markers for vascular inflammation. High miR-19a expression was associated with reduced TF protein, TF-mediated procoagulability, and vascular inflammation based on expression of vascular adhesion molecule-1 and leukocyte count. We found plasma expression of miR-19a to strongly correlate with miR-126. miR-19a reduced the TF expression on mRNA and protein level in human microvascular endothelial cells (HMEC) as well as TF activity in human monocytes (THP-1), while anti-miR-19a increased the TF expression. Interestingly, miR-19a induced VCAM expression in HMEC. However, miR-19a and miR-126 co-transfection reduced total endothelial VCAM expression and exhibited additive inhibition of a luciferase reporter construct containing the F3 3′UTR. Conclusions While both miRs have differential functions on endothelial VCAM expression, miR-19a and miR-126 cooperate to exhibit anti-thrombotic properties via regulating vascular TF expression. Modulating the post-transcriptional control of TF in diabetes may provide a future anti-thrombotic and anti-inflammatory therapy. |
| first_indexed | 2024-12-19T22:56:06Z |
| format | Article |
| id | doaj.art-bfaaf58c38c94a8ab35838e4a40faf5f |
| institution | Directory Open Access Journal |
| issn | 1475-2840 |
| language | English |
| last_indexed | 2024-12-19T22:56:06Z |
| publishDate | 2018-02-01 |
| publisher | BMC |
| record_format | Article |
| series | Cardiovascular Diabetology |
| spelling | doaj.art-bfaaf58c38c94a8ab35838e4a40faf5f2022-12-21T20:02:38ZengBMCCardiovascular Diabetology1475-28402018-02-0117111110.1186/s12933-018-0678-zMicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetesMarco Witkowski0Termeh Tabaraie1Daniel Steffens2Julian Friebel3Andrea Dörner4Carsten Skurk5Mario Witkowski6Bernd Stratmann7Diethelm Tschoepe8Ulf Landmesser9Ursula Rauch10Charité Centrum 11, Depart. of Cardiology, Campus Benjamin Franklin, Charité University Medicine BerlinCharité Centrum 11, Depart. of Cardiology, Campus Benjamin Franklin, Charité University Medicine BerlinCharité Centrum 11, Depart. of Cardiology, Campus Benjamin Franklin, Charité University Medicine BerlinCharité Centrum 11, Depart. of Cardiology, Campus Benjamin Franklin, Charité University Medicine BerlinCharité Centrum 11, Depart. of Cardiology, Campus Benjamin Franklin, Charité University Medicine BerlinCharité Centrum 11, Depart. of Cardiology, Campus Benjamin Franklin, Charité University Medicine BerlinInstitute of Microbiology and Infection Immunology, Charité University Medicine BerlinHeart and Diabetes Center NRW, Ruhr University of BochumHeart and Diabetes Center NRW, Ruhr University of BochumCharité Centrum 11, Depart. of Cardiology, Campus Benjamin Franklin, Charité University Medicine BerlinCharité Centrum 11, Depart. of Cardiology, Campus Benjamin Franklin, Charité University Medicine BerlinAbstract Background Diabetes mellitus is characterized by chronic vascular disorder and presents a main risk factor for cardiovascular mortality. In particular, hyperglycaemia and inflammatory cytokines induce vascular circulating tissue factor (TF) that promotes pro-thrombotic conditions in diabetes. It has recently become evident that alterations of the post-transcriptional regulation of TF via specific microRNA(miR)s, such as miR-126, contribute to the pathogenesis of diabetes and its complications. The endothelial miR-19a is involved in vascular homeostasis and atheroprotection. However, its role in diabetes-related thrombogenicity is unknown. Understanding miR-networks regulating procoagulability in diabetes may help to develop new treatment options preventing vascular complications. Methods and results Plasma of 44 patients with known diabetes was assessed for the expression of miR-19a, TF protein, TF activity, and markers for vascular inflammation. High miR-19a expression was associated with reduced TF protein, TF-mediated procoagulability, and vascular inflammation based on expression of vascular adhesion molecule-1 and leukocyte count. We found plasma expression of miR-19a to strongly correlate with miR-126. miR-19a reduced the TF expression on mRNA and protein level in human microvascular endothelial cells (HMEC) as well as TF activity in human monocytes (THP-1), while anti-miR-19a increased the TF expression. Interestingly, miR-19a induced VCAM expression in HMEC. However, miR-19a and miR-126 co-transfection reduced total endothelial VCAM expression and exhibited additive inhibition of a luciferase reporter construct containing the F3 3′UTR. Conclusions While both miRs have differential functions on endothelial VCAM expression, miR-19a and miR-126 cooperate to exhibit anti-thrombotic properties via regulating vascular TF expression. Modulating the post-transcriptional control of TF in diabetes may provide a future anti-thrombotic and anti-inflammatory therapy.http://link.springer.com/article/10.1186/s12933-018-0678-zDiabetes mellitusTissue factorMicroRNA 19aCoagulationVascular inflammation |
| spellingShingle | Marco Witkowski Termeh Tabaraie Daniel Steffens Julian Friebel Andrea Dörner Carsten Skurk Mario Witkowski Bernd Stratmann Diethelm Tschoepe Ulf Landmesser Ursula Rauch MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes Cardiovascular Diabetology Diabetes mellitus Tissue factor MicroRNA 19a Coagulation Vascular inflammation |
| title | MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes |
| title_full | MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes |
| title_fullStr | MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes |
| title_full_unstemmed | MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes |
| title_short | MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes |
| title_sort | microrna 19a contributes to the epigenetic regulation of tissue factor in diabetes |
| topic | Diabetes mellitus Tissue factor MicroRNA 19a Coagulation Vascular inflammation |
| url | http://link.springer.com/article/10.1186/s12933-018-0678-z |
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