The Emerging Role of MiR-223 in Platelet Reactivity: Implications in Antiplatelet Therapy

Overview

Journal Biomed Res Int

Publisher Wiley

Specialties Biomedical Engineering
Biotechnology
General Medicine

Date 2015 Jul 30

PMID 26221610

Citations 28

Authors

Rui Shi

Xin Zhou

Wen-Jie Ji

Ying-Ying Zhang

Yong-Qiang Ma

Jian-Qi Zhang

Yu-Ming Li

Affiliations

Soon will be listed here.

Abstract

Platelets are anuclear cells and are devoid of genomic DNA, but they are capable of de novo protein synthesis from mRNA derived from their progenitor cells, megakaryocytes. There is mounting evidence that microRNA (miRNA) plays an important role in regulating gene expression in platelets. miR-223 is the most abundant miRNAs in megakaryocytes and platelets. One of the miR-223-regulated genes is ADP P2Y12, a key target for current antiplatelet drug therapy. Recent studies showed that a blunted response to P2Y12 antagonist, that is, high on-treatment platelet reactivity (HTPR), is a strong predictor of major cardiovascular events (MACEs) in coronary heart disease (CHD) patients receiving antiplatelet treatment. Recent clinical cohort study showed that the level of circulating miR-223 is inversely associated with MACE in CHD patients. In addition, our recent data demonstrated that the level of both intraplatelet and circulating miR-223 is an independent predictor for HTPR, thus providing a link between miR-223 and MACE. These lines of evidence indicate that miR-223 may serve as a potential regulatory target for HTPR, as well as a diagnostic tool for identification of HTPR in clinical settings.

Citing Articles

The Platelet-Specific Gene Signature in the Immunoglobulin G4-Related Disease Transcriptome.

Oguz A, Oygur C, Gur Dedeoglu B, Dogan Turacli I, Serin Kilicoglu S, Ergun I Medicina (Kaunas). 2025; 61(1).

PMID: 39859144 PMC: 11767091. DOI: 10.3390/medicina61010162.

Epigenetic Biomarkers in Thrombophilia-Related Pregnancy Complications: Mechanisms, Diagnostic Potential, and Therapeutic Implications: A Narrative Review.

Bardan C, Ionita I, Iordache M, Calamar-Popovici D, Todorescu V, Popescu R Int J Mol Sci. 2025; 25(24.

PMID: 39769397 PMC: 11728153. DOI: 10.3390/ijms252413634.

Platelet-enriched microRNAs as novel biomarkers in atherosclerotic and cardiovascular disease patients.

Masoudikabir P, Shirazy M, Taghizadeh F, Gheydari M, Hamidpour M ARYA Atheroscler. 2024; 20(4):47-67.

PMID: 39717424 PMC: 11663285. DOI: 10.48305/arya.2024.41664.2898.

Topographic Distribution of miRNAs (miR-30a, miR-223, miR-let-7a, miR-let-7f, miR-451, and miR-486) in the Plasma Extracellular Vesicles.

Petrova T, Kalinina O, Aquino A, Grigoryev E, Dubashynskaya N, Zubkova K Noncoding RNA. 2024; 10(1).

PMID: 38392970 PMC: 10892389. DOI: 10.3390/ncrna10010015.

Platelet microRNAs as Potential Novel Biomarkers for Antiplatelet Therapy with P2Y Inhibitors and Their Association with Platelet Function.

Gumiezna K, Bednarek A, Sygitowicz G, Maciejak-Jastrzebska A, Barus P, Hunia J J Clin Med. 2024; 13(1).

PMID: 38202070 PMC: 10780110. DOI: 10.3390/jcm13010063.

References

Kondkar A, Bray M, Leal S, Nagalla S, Liu D, Jin Y . VAMP8/endobrevin is overexpressed in hyperreactive human platelets: suggested role for platelet microRNA. J Thromb Haemost. 2009; 8(2):369-78. PMC: 3312605. DOI: 10.1111/j.1538-7836.2009.03700.x. View

Zardo G, Ciolfi A, Vian L, Starnes L, Billi M, Racanicchi S . Polycombs and microRNA-223 regulate human granulopoiesis by transcriptional control of target gene expression. Blood. 2012; 119(17):4034-46. DOI: 10.1182/blood-2011-08-371344. View

Engelmann B, Massberg S . Thrombosis as an intravascular effector of innate immunity. Nat Rev Immunol. 2012; 13(1):34-45. DOI: 10.1038/nri3345. View

Shi R, Ge L, Zhou X, Ji W, Lu R, Zhang Y . Decreased platelet miR-223 expression is associated with high on-clopidogrel platelet reactivity. Thromb Res. 2013; 131(6):508-13. DOI: 10.1016/j.thromres.2013.02.015. View

Berger J, Bhatt D, Steinhubl S, Shao M, Steg P, Montalescot G . Smoking, clopidogrel, and mortality in patients with established cardiovascular disease. Circulation. 2009; 120(23):2337-44. PMC: 2814172. DOI: 10.1161/CIRCULATIONAHA.109.866533. View

Leierseder S, Petzold T, Zhang L, Loyer X, Massberg S, Engelhardt S . MiR-223 is dispensable for platelet production and function in mice. Thromb Haemost. 2013; 110(6):1207-14. DOI: 10.1160/TH13-07-0623. View

Fabian M, Sundermeier T, Sonenberg N . Understanding how miRNAs post-transcriptionally regulate gene expression. Prog Mol Subcell Biol. 2009; 50:1-20. DOI: 10.1007/978-3-642-03103-8_1. View

Urbich C, Kuehbacher A, Dimmeler S . Role of microRNAs in vascular diseases, inflammation, and angiogenesis. Cardiovasc Res. 2008; 79(4):581-8. DOI: 10.1093/cvr/cvn156. View

Zhuang G, Meng C, Guo X, Cheruku P, Shi L, Xu H . A novel regulator of macrophage activation: miR-223 in obesity-associated adipose tissue inflammation. Circulation. 2012; 125(23):2892-903. DOI: 10.1161/CIRCULATIONAHA.111.087817. View

10.

Bugert P, Dugrillon A, Gunaydin A, Eichler H, Kluter H . Messenger RNA profiling of human platelets by microarray hybridization. Thromb Haemost. 2003; 90(4):738-48. View

11.

Fazi F, Rosa A, Fatica A, Gelmetti V, De Marchis M, Nervi C . A minicircuitry comprised of microRNA-223 and transcription factors NFI-A and C/EBPalpha regulates human granulopoiesis. Cell. 2005; 123(5):819-31. DOI: 10.1016/j.cell.2005.09.023. View

12.

Ang L, Palakodeti V, Khalid A, Tsimikas S, Idrees Z, Tran P . Elevated plasma fibrinogen and diabetes mellitus are associated with lower inhibition of platelet reactivity with clopidogrel. J Am Coll Cardiol. 2008; 52(13):1052-9. DOI: 10.1016/j.jacc.2008.05.054. View

13.

Fichtlscherer S, Zeiher A, Dimmeler S . Circulating microRNAs: biomarkers or mediators of cardiovascular diseases?. Arterioscler Thromb Vasc Biol. 2011; 31(11):2383-90. DOI: 10.1161/ATVBAHA.111.226696. View

14.

Diehl P, Fricke A, Sander L, Stamm J, Bassler N, Htun N . Microparticles: major transport vehicles for distinct microRNAs in circulation. Cardiovasc Res. 2012; 93(4):633-44. PMC: 3291092. DOI: 10.1093/cvr/cvs007. View

15.

Zeman M, Cimprich K . Causes and consequences of replication stress. Nat Cell Biol. 2013; 16(1):2-9. PMC: 4354890. DOI: 10.1038/ncb2897. View

16.

Chen C, Li L, Lodish H, Bartel D . MicroRNAs modulate hematopoietic lineage differentiation. Science. 2003; 303(5654):83-6. DOI: 10.1126/science.1091903. View

17.

Curtis A, FitzGerald G . Platelet microRNAs: Novy Mir* or mired in human complexity?. Circ Res. 2013; 112(4):576-8. DOI: 10.1161/CIRCRESAHA.113.300859. View

18.

Lee Y, Ahn C, Han J, Choi H, Kim J, Yim J . The nuclear RNase III Drosha initiates microRNA processing. Nature. 2003; 425(6956):415-9. DOI: 10.1038/nature01957. View

19.

Wienholds E, Kloosterman W, Miska E, Alvarez-Saavedra E, Berezikov E, de Bruijn E . MicroRNA expression in zebrafish embryonic development. Science. 2005; 309(5732):310-1. DOI: 10.1126/science.1114519. View

20.

Jamaluddin M, Weakley S, Zhang L, Kougias P, Lin P, Yao Q . miRNAs: roles and clinical applications in vascular disease. Expert Rev Mol Diagn. 2010; 11(1):79-89. PMC: 3077058. DOI: 10.1586/erm.10.103. View