MicroRNA-19a contributes to the epigenetic regulation of tissue factor in diabetes.
Cardiovasc Diabetol
; 17(1): 34, 2018 02 24.
Article
en En
| MEDLINE
| ID: mdl-29477147
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 ANDRESULTS:
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.Palabras clave
Texto completo:
1
Bases de datos:
MEDLINE
Asunto principal:
Trombosis
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Coagulación Sanguínea
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Tromboplastina
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MicroARNs
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Epigénesis Genética
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Diabetes Mellitus
Tipo de estudio:
Diagnostic_studies
/
Risk_factors_studies
Límite:
Aged
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Female
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Humans
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Male
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Middle aged
Idioma:
En
Revista:
Cardiovasc Diabetol
Asunto de la revista:
ANGIOLOGIA
/
CARDIOLOGIA
/
ENDOCRINOLOGIA
Año:
2018
Tipo del documento:
Article
País de afiliación:
Alemania