Micro–RNA-126 Reduces the Blood Thrombogenicity in Diabetes Mellitus via Targeting of Tissue Factor
Open accessAbstract
Objective—: Diabetes mellitus involves vascular inflammatory processes and is a main contributor to cardiovascular mortality. Notably, heightened levels of circulating tissue factor (TF) account for the increased thrombogenicity and put those patients at risk for thromboembolic events. Here, we sought to investigate the role of micro-RNA (miR)–driven TF expression and thrombogenicity in diabetes mellitus. Approach and Results—: Plasma samples of patients with diabetes mellitus were analyzed for TF protein and activity as well as miR-126 expression before and after optimization of the antidiabetic treatment. We found low miR-126 levels to be associated with markedly increased TF protein and TF-mediated thrombogenicity. Reduced miR-126 expression was accompanied by increased vascular inflammation as evident from the levels of vascular adhesion molecule-1 and fibrinogen, as well as leukocyte counts. With optimization of the antidiabetic treatment miR-126 levels increased and thrombogenicity was reduced. Using a luciferase reporter system, we demonstrated miR-126 to directly bind to the F3 -3′-untranslated region, thereby reducing TF expression both on mRNA and on protein levels in human microvascular endothelial cells as well as TF mRNA and activity in monocytes. Conclusions—: Circulating miR-126 exhibits antithrombotic properties via regulating post-transcriptional TF expression, thereby impacting the hemostatic balance of the vasculature in diabetes mellitus.
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Vascular tissue factor promotes thrombosis and vascular inflammation, particularly in patients with type 2 diabetes who have higher levels of circulating trimethylamine N-oxide.
“Vascular TF promotes thrombosis and vascular inflammation123, particularl y in patients with type 2 diabetes who have higher levels of circulating TMAO124–126.”
From Gut microbiota and cardiovascular disease. (2020) · cites this paper as [125]
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- Authors
- Witkowski, M., Weithauser, A., Tabaraie, T., Steffens, D., Kränkel, N., Witkowski, M., Stratmann, B., Tschoepe, D., Landmesser, U., & Rauch-Kroehnert, U.
- Affiliations
- Johannes Gutenberg University Mainz (DE)
- From the Charité Centrum 11, Department of Cardiology, Charité–Universitätsmedizin, Berlin, Germany; Research Centre Immunology and Institute of Medical Microbiology and Hygiene, University of Mainz Medical Centre, Mainz, Germany; and Heart and Diabetes Center NRW, Ruhr University of Bochum, Bad Oeynhausen, Germany.
- Heart and Diabetes Center North Rhine-Westphalia (DE)
- Corresponding author
- Rauch-Kroehnert, Ursula
- ORCID
- Venue
- Arteriosclerosis, Thrombosis, and Vascular Biology
- Published
- 2016-06
- Volume
- 36
- Issue
- 6
- Pages
- 1263-1271
- ISSN
- 1079-5642 (ISSN-L)
- 1524-4636
- PMC
- PMC4894779
- OpenAlex
- W2344258676
- Cited by
- 79
- References
- 43
- Citations by year
- 2025: 4 · 2024: 2 · 2023: 14 · 2022: 10 · 2021: 11 · 2020: 14 · 2019: 2 · 2018: 8 · 2017: 10 · 2016: 4
- FWCI
- 3.34
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by
- Locations
- Arteriosclerosis Thrombosis and Vascular Biology (publishedVersion, cc-by)
- Europe PMC (PubMed Central) (publishedVersion, cc-by)
- PubMed Central (publishedVersion, cc-by)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Cancer Research › MicroRNA in disease regulation
- Health Sciences › Medicine › Hematology › Blood Coagulation and Thrombosis Mechanisms
- Health Sciences › Medicine › Pulmonary and Respiratory Medicine › Blood properties and coagulation
- Keywords
- miR-126, tissue factor, diabetes mellitus, thrombogenicity, microRNA regulation, post-transcriptional regulation, vascular inflammation, diabetes treatment, endothelial cells, monocytes, hemostasis, fibrinogen
- MeSH terms
- Aged, Binding Sites, Cell Line, Diabetes Mellitus, Female, Fibrinogen, Gene Expression Regulation, Hemostasis, Humans, Hypoglycemic Agents, Male, Middle Aged, Monocytes, Thromboplastin, Thrombosis, Time Factors, Transfection, Genes, Reporter, Vascular Cell Adhesion Molecule-1, 3' Untranslated Regions, RNA Interference, MicroRNAs, Endothelial Cells
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