A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears
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Authors
Fazzalari, AmandaBasadonna, Giacomo
Kucukural, Alper
Tanriverdi, Kahraman
Koupenova-Zamor, Milka
Dickson, Eric W.
Blackwood, Meghan
Mueller, Christian
Freedman, Jane E.
Cahan, Mitchell A.
UMass Chan Affiliations
Department of PediatricsMueller Lab for Gene Therapy, Horae Gene Therapy Center
Department of Emergency Medicine
Division of Cardiovascular Medicine, Department of Medicine
Program in Molecular Medicine
Bioinformatics Core
Department of Surgery
Document Type
Journal ArticlePublication Date
2020-08-25Keywords
AnticoagulationAntithrombin
Thrombosis
Venous thromboembolism
microRNA
Biological Phenomena, Cell Phenomena, and Immunity
Cardiovascular Diseases
Circulatory and Respiratory Physiology
Disease Modeling
Genetics and Genomics
Molecular Biology
Nucleic Acids, Nucleotides, and Nucleosides
Physiological Processes
Surgery
Translational Medical Research
Metadata
Show full item recordAbstract
BACKGROUND: Hibernating American black bears have significantly different clotting parameters than their summer active counterparts, affording them protection against venous thromboembolism during prolonged periods of immobility. We sought to evaluate if significant differences exist between the expression of microRNAs in the plasma of hibernating black bears compared with their summer active counterparts, potentially contributing to differences in hemostasis during hibernation. MATERIALS AND METHODS: MicroRNA sequencing was assessed in plasma from 21 American black bears in summer active (n = 11) and hibernating states (n = 10), and microRNA signatures during hibernating and active state were established using both bear and human genome. MicroRNA targets were predicted using messenger RNA (mRNA) transcripts from black bear kidney cells. In vitro studies were performed to confirm the relationship between identified microRNAs and mRNA expression, using artificial microRNA and human liver cells. RESULTS: Using the bear genome, we identified 15 microRNAs differentially expressed in the plasma of hibernating black bears. Of these microRNAs, three were significantly downregulated (miR-141-3p, miR-200a-3p, and miR-200c-3p), were predicted to target SERPINC1, the gene for antithrombin, and demonstrated regulatory control of the gene mRNA expression in cell studies. CONCLUSIONS: Our findings suggest that the hibernating black bears' ability to maintain hemostasis and achieve protection from venous thromboembolism during prolonged periods of immobility may be due to changes in microRNA signatures and possible upregulation of antithrombin expression.Source
Fazzalari A, Basadonna G, Kucukural A, Tanriverdi K, Koupenova M, Pozzi N, Kakuturu J, Friedrich AU, Korstanje R, Fowler N, Belant JL, Beyer DE Jr, Brooks MB, Dickson EW, Blackwood M, Mueller C, Palesty JA, Freedman JE, Cahan MA. A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears. J Surg Res. 2020 Aug 25;257:203-212. doi: 10.1016/j.jss.2020.06.027. Epub ahead of print. PMID: 32858321. Link to article on publisher's site
DOI
10.1016/j.jss.2020.06.027Permanent Link to this Item
http://hdl.handle.net/20.500.14038/29578PubMed ID
32858321Notes
Full author list omitted for brevity. For the full list of authors, see article.
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10.1016/j.jss.2020.06.027