Abstract 15695: Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice
Background: MicroRNA (miR)-223 is highly expressed in platelets (PLT) and may serve as a biomarker of PLT activation. Some studies have shown that plasma levels of miR-223 are reduced following inhibition of PLT function, while others have shown a correlation between low plasma miR-223 levels and high on-treatment PLT reactivity. The present study is to investigate the role of miR-223 on arterial thrombosis following endothelial injury.
Methods and Results: A model of rose bengal-induced photochemical injury was performed on carotid arteries of male C57BL/6 (C57B6), B6.SJL-Ptprca Pepcb/BoyJ (B6.SJL), and miR-223 deficient mice on C57B6-B6.SJL genetic background. Following carotid injury, miR-223 deficient mice showed significantly prolonged times to occlusive thrombosis compared to C57BL/6 and B6.SJL mice (90.0±5.4 vs 44.7±5.7 and 40.8±5.0 mins. n=6 per group, p<0.01), indicating a protective effect of miR-223 deficiency on thrombosis in this model. PLT counts were lower in miR-223 deficient mice (644.6±54.2 x 103/[[Unsupported Character - Symbol Font ]]l) compared with C57B6 and B6.SJL mice (901.8±67.1 x 103/[[Unsupported Character - Symbol Font ]]l and 896.8±30.3 x 103/[[Unsupported Character - Symbol Font ]]l) (n=5 per group, P<0.05). To determine whether the hematopoietic pool of miR-223 was responsible for this thrombosis phenotype, bone marrow transplantation (BMT) was performed from miR-223 deficient mice into C57B6 recipients, and compared to control C57BL/6 recipient mice that received C57B6 BM. 8-10 weeks following BMT, PLT counts were lower in mice receiving miR-223 deficient BM compared to mice receiving C57B6 BM (785.2±25.9 x 103/[[Unsupported Character - Symbol Font ]]l vs 925.4±21.1 x 103/[[Unsupported Character - Symbol Font ]]l, n=5 per group, p<0.01), while RBC and WBC counts were similar. Time to occlusive thrombosis was prolonged in mice receiving miR-223 deficient BM compared to mice receiving C57BL/6 BM (87.0±5.8 vs 50.0±4.3 mins, n=10 per group, p<0.01).
Conclusion: Hematopoietic miR-223 is a potent regulator of arterial thrombosis following endothelial injury. This study indicates that miR-223 is a potential therapeutic target for prevention of arterial thrombosis.
Author Disclosures: H. Wang: None. W. Luo: None. J. Wang: None. C. Guo: None. N. Kaissarian: None. D.T. Eitzman: None.
- © 2014 by American Heart Association, Inc.