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Semin Thromb Hemost 2021; 47(08): 982-991
DOI: 10.1055/s-0041-1726341
Review Article

MiRNA 126 as a New Predictor Biomarker in Venous Thromboembolism of Persistent Residual Vein Obstruction: A Review of the Literature Plus a Pilot Study

Pietro Rossetti
1   Department of Internal Medicine, Angiology and Coagulation Unit, University Hospital of Parma, Parma, Italy
,
Matteo Goldoni
2   Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy
,
Vittorio Pengo
3   Department of Cardiac, Thoracic and Vascular Sciences, University of Padua, Padua, Italy
,
Rosanna Vescovini
4   Department of Clinical and Experimental Medicine, University Hospital of Parma, Parma, Italy
,
Paola Mozzoni
2   Department of Medicine and Surgery, University Hospital of Parma, Parma, Italy
,
Maria Ilaria Tassoni
1   Department of Internal Medicine, Angiology and Coagulation Unit, University Hospital of Parma, Parma, Italy
,
Maria Lombardi
1   Department of Internal Medicine, Angiology and Coagulation Unit, University Hospital of Parma, Parma, Italy
,
Pasquale Rubino
1   Department of Internal Medicine, Angiology and Coagulation Unit, University Hospital of Parma, Parma, Italy
,
Gino Bernuzzi
5   Immunohematology and Transfusion Center, University Hospital of Parma, Parma, Italy
,
Ignazio Verzicco
4   Department of Clinical and Experimental Medicine, University Hospital of Parma, Parma, Italy
,
Cesare Manotti
1   Department of Internal Medicine, Angiology and Coagulation Unit, University Hospital of Parma, Parma, Italy
,
Roberto Quintavalla
1   Department of Internal Medicine, Angiology and Coagulation Unit, University Hospital of Parma, Parma, Italy
› Author Affiliations Funding The study received financial support from the University of Parma.
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Abstract

Venous thromboembolism (VTE) is the third most common cardiovascular disease. Interleukins (ILs) and micro-ribonucleic acids (miRNAs) have been proposed as molecules able to modulate endothelial inflammation and platelet hyperactivity. At present, no early biomarkers are available to predict the outcome of VTE. We investigated in a pilot study a selected number of miRNAs and ILs as prognostic VTE biomarkers and reviewed literature in this setting. Twenty-three patients (aged 18–65) with a new diagnosis of non-oncological VTE and free from chronic inflammatory diseases were enrolled. Twenty-three age- and sex-matched healthy blood donors were evaluated as control subjects. Serum miRNAs (MiRNA 126, 155, 17.92, 195), inflammatory cytokines (IL-6, tumor necrosis factor-α, IL-8), and lymphocyte subsets were evaluated in patients at enrolment (T0) and in controls. In VTE patients, clinical and instrumental follow-up were performed assessing residual vein obstruction, miRNA and ILs evaluation at 3 months' follow-up (T1). At T0, IL-8, activated T lymphocytes, Treg lymphocytes, and monocytes were higher in patients compared with healthy controls, as were miRNA 126 levels. Moreover, miRNA 126 and IL-6 were significantly increased at T0 compared with T1 evaluation in VTE patients. Higher levels of MiR126 at T0 correlated with a significant overall thrombotic residual at follow-up. In recent years an increasing number of studies (case–control studies, in vivo studies in animal models, in vitro studies) have suggested the potential role of miRNAs in modulating the cellular and biohumoral responses involved in VTE. In the frame of epidemiological evidence, this pilot study with a novel observational approach supports the notion that miRNA can be diagnostic biomarkers of VTE and first identifies miRNA 126 as a predictor of outcome, being associated with poor early recanalization.

Keywords

micro-RNA - immunothrombosis - deep vein thromboembolism - residual vein obstruction - prognostic biomarker

Authors' contributions

P.R. contributed to concept and design the study, data collection, interpretation of data, writing, and revising the intellectual content of the manuscript; M.G. contributed to statistical analysis; V.P. and R.Q. contributed to revise the intellectual content of the manuscript; R.V. contributed to analyze data and immunophenotyping evaluation; P.M. contributed to analyze data and miRNA detection; M.I.T., M.L., P.R., G.B., C.M., and I.V. contributed to collect clinical data. All the authors contributed to revise the manuscript and gave the final approval of the version to be published.




Publication History

Article published online:
09 July 2021

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