Thromb Haemost 2019; 119(09): 1451-1460
DOI: 10.1055/s-0039-1692681
Cellular Haemostasis and Platelets
Georg Thieme Verlag KG Stuttgart · New York

miR-34b-3p May Promote Antiplatelet Efficiency of Aspirin by Inhibiting Thromboxane Synthase Expression

Wen Wen Liu
1   Department of Geriatrics, Peking University First Hospital, Xicheng District, Beijing, China
,
Hao Wang
1   Department of Geriatrics, Peking University First Hospital, Xicheng District, Beijing, China
,
Xia Huan Chen
1   Department of Geriatrics, Peking University First Hospital, Xicheng District, Beijing, China
,
Sidney W. Fu
2   Division of Genomic Medicine, Department of Medicine, The George Washington University School of Medicine and Health Sciences, Washington, District of Columbia, United States
,
Mei Lin Liu
1   Department of Geriatrics, Peking University First Hospital, Xicheng District, Beijing, China
› Author Affiliations
Funding This study was supported by the International Science & Technology Cooperation Project of China (2013DFA30860). The funding source was the government agency, which played no role in the collection, analysis, and interpretation of data or the preparation of the manuscript.
Further Information

Publication History

15 January 2019

07 May 2019

Publication Date:
02 July 2019 (online)

Abstract

Aspirin has been widely used for the prevention of cardiovascular diseases, but its antiplatelet efficiency varies between individuals. The present study aimed to evaluate response to aspirin based on gene profiles as well as potential regulating pathways using human blood samples and cell lines. Platelet function in patients 50 years or older with coronary artery disease on 100 mg/day aspirin was measured by light transmission aggregometry (LTA) of arachidonic acid (AA)-induced platelet aggregation. The expression of eight candidate genes—PTGS1/COX1, PLA2G4A, PLA2G6, PLA2G7, TBXAS1, TBXA2R, PTGIR, and ITGA2B—and the ingredients involved in AA metabolism were analyzed. Our data showed that the expressions of thromboxane A synthase 1 (TBXAS1), thromboxane synthase (TXS), and thromboxane B2 (TXB2) were increased in the upper quartile of platelet aggregation (LTA-AA_Q4) group compared with the lower quartile of platelet aggregation (LTA-AA_Q1) group. Our bioinformatics analysis suggested that TBXAS1 was targeted by miR-34b-3p via binding to its 3′-UTR, which was subsequently verified experimentally. Although overexpression of miR-34b-3p exhibited no apparent effect on cell proliferation, inhibition of miR-34b-3p promoted megakaryocyte viability. Our data demonstrated that the expression of TBXAS1 was higher in the aspirin hyporesponsiveness group than that in the hyperresponsiveness group, suggesting that high expression of TBXAS1 may be associated with aspirin hyporesponsiveness. miR-34b-3p may regulate the platelet and aspirin response by suppressing TBXAS1 expression and megakaryocyte proliferation.

Authors' Contributions

WW.L developed an overall research plan, collected samples together with clinical data, performed experiments, and wrote the paper; H.W. assisted with the experiments of protein extraction and Western blot assays; XH.C provided essential medical records; SW.F interpreted the data and revised the manuscript; ML.L directed the overall project, interpreted the data, and revised the manuscript.


Supplementary Material

 
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