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Therapeutic implication of MicroRNA-320a antagonist in attenuating blood clots formed during venous thrombosis

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Abstract

Venous thrombosis (VT) is a complex multi-factorial disease and a major health concern worldwide. Its clinical implications include deep vein thrombosis (DVT) and pulmonary embolism (PE). VT pathogenesis involves intricate interplay of various coagulants and anti-coagulants. Growing evidences from epidemiological studies have shown that many non-coding microRNAs play significant regulatory role in VT pathogenesis by modulating expressions of large number of gene involved in blood coagulation. Present study aimed to investigate the effect of human micro RNA (hsa-miR)-320a antagonist on thrombus formation in VT. Surgery was performed on Sprague–Dawley (SD) rats, wherein the inferior vena cava (IVC) was ligated to introduce DVT. Animals were divided into four groups (n = 5 in each group); Sham controls (Sham), IVC ligated-DVT (DVT), IVC ligated-DVT + transfection reagent (DVT-NC) and IVC ligated-DVT + miR320a antagonist (DVT-miR-320a antagonist). IVC was dissected after 6 h and 24 h of surgery to estimate thrombus weight and coagulatory parameters such as levels of D-dimer, clotting time and bleeding time. Also, ELISA based biochemical assays were formed to assess toxicity of miRNA antagonist in animals. Our experimental analysis demonstrated that there was a marked reduction in size of thrombus in hsa-miR-320a antagonist treated animals, both at 6 h and 24 h. There was a marked reduction in D-dimer levels in hsa-miR-320a antagonist treated animals. Also, blood clotting time was delayed and bleeding time was increased significantly in hsa-miR-320a antagonist treated rats compared to the non-treated and Sham rats. There was no sign of toxicity in treated group compared to control animals. Hsa-miR-320a antagonist could be promising therapeutic target for management of VT.

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Data availability

The datasets used and analyzed during the current study available from the corresponding author on reasonable request.

Abbreviations

BT:

Bleeding time

CT:

Clotting time

DVT:

Deep vein thrombosis

IVC:

Inferior vena cava

PE:

Pulmonary embolism

VT:

Venous thrombosis

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Acknowledgements

The authors are extremely thankful to Animal house of DIPAS for providing healthy animals for the study. Authors also acknowledge efforts and cooperation of technical staff and research scholars during the experiments.

Funding

Defence Institute of Physiology and Allied Sciences (DIPAS), Defence Research and Development Organization (DRDO), S&T(A)/22-23/DIP-276.

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  1. Pathophysiology and Disruptive Technology Division (PDT), Defence Research and Development Organization (DRDO), Defence Institute of Physiology and Allied Sciences (DIPAS), Lucknow Road, Timarpur, Delhi, 110054, India

    Swati Srivastava, Iti Garg, Nilanjana Ghosh & Rajeev Varshney

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  1. Swati Srivastava
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SS: experiment design, analysis and manuscript writing; IG and NG: experimental work and analysis; RV: review and editing of manuscript.

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Correspondence to Swati Srivastava.

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Srivastava, S., Garg, I., Ghosh, N. et al. Therapeutic implication of MicroRNA-320a antagonist in attenuating blood clots formed during venous thrombosis. J Thromb Thrombolysis 57, 699–709 (2024). https://doi.org/10.1007/s11239-024-02947-6

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