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A Translational Model for Venous Thromboembolism: MicroRNA Expression in Hibernating Black Bears
Amanda Fazzalari1, Giacomo Basadonna2, Alper Kucukural3
1Department of Surgery, University of Massachusetts Medical School, Worcester, Massachusetts; The Stanley J. Dudrick Department of Surgery, Saint Mary's Hospital, Waterbury, Connecticut.
The Journal of Surgical Research
|August 29, 2020
Summary
Hibernating black bears show altered microRNA (miRNA) levels, potentially explaining their protection against blood clots during immobility. Downregulated miRNAs may increase antithrombin, aiding hemostasis.
Area of Science:
- Comparative genomics
- Molecular biology
- Physiology
Background:
- Hibernating American black bears exhibit distinct clotting parameters compared to active bears.
- These hemostatic differences may protect against venous thromboembolism during prolonged inactivity.
Purpose of the Study:
- To investigate differential microRNA (miRNA) expression in the plasma of hibernating versus active American black bears.
- To determine if miRNA expression changes contribute to altered hemostasis during hibernation.
Main Methods:
- Plasma microRNA sequencing in 21 American black bears (11 active, 10 hibernating).
- Identification of miRNA signatures using bear and human genomes.
- In vitro studies to validate miRNA-mRNA regulatory relationships and target prediction using black bear kidney cell mRNA.
Main Results:
- Fifteen differentially expressed miRNAs were identified in hibernating bears.
- Three miRNAs (miR-141-3p, miR-200a-3p, miR-200c-3p) were significantly downregulated.
- These downregulated miRNAs were predicted to target SERPINC1 (antithrombin) and showed regulatory control in cell studies.
Conclusions:
- Altered miRNA signatures in hibernating bears may contribute to hemostasis.
- Potential upregulation of antithrombin expression, mediated by downregulated miRNAs, could explain protection from venous thromboembolism during immobility.
