Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice
| Autor: | Daniel T. Eitzman, Hui Wang, Kyle Kleiman, Qian Wang, Chiao Guo |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Male medicine.medical_specialty Time Factors Science 030204 cardiovascular system & hematology Article Receptor IGF Type 1 03 medical and health sciences 0302 clinical medicine mir-223 Internal medicine microRNA medicine Deficient mouse Animals Platelet Receptor Regulation of gene expression Multidisciplinary business.industry Endothelial Cells Thrombosis medicine.disease Photochemical Processes Hematopoiesis Mice Inbred C57BL Haematopoiesis MicroRNAs 030104 developmental biology Endocrinology Carotid Arteries Gene Expression Regulation Immunology Medicine Female business |
| Zdroj: | Scientific Reports Scientific Reports, Vol 7, Iss 1, Pp 1-7 (2017) |
| ISSN: | 2045-2322 |
| Popis: | Some studies have shown that levels of MicroRNA (miR)-223 derived from platelets in the plasma are reduced following inhibition of platelet function, while others have shown a correlation between low plasma miR-223 and high on-treatment platelet reactivity. The present study seeks to investigate the role of miR-223 in arterial thrombosis. A model of photochemical-induced carotid thrombosis was applied to miR-223 deficient mice and littermate (WT) controls. Mice deficient in miR-223 exhibited significantly prolonged times to occlusive thrombosis compared to WT mice indicating a protective effect of miR-223 deficiency. Bone marrow transplantation experiments confirmed that the hematopoietic pool of miR-223 was responsible for differences in thrombosis times. Transfusion of either WT platelets or extracellular vesicles derived from WT platelets were both sufficient to shorten thrombosis times in miR-223 deficient recipients. The effect of platelet transfusions on IGF-1R was explored. These experiments revealed that vascular IGF-1R was down-regulated by platelet miR-223. Furthermore, inhibition of IGF-1R abolished the protection conferred by miR-223 deficiency on thrombosis. In conclusion, platelet miR-223 is a regulator of arterial thrombosis following endothelial injury through effects on vascular wall IGF-1R. This study indicates that platelet miR-223 is a potential therapeutic target for prevention of arterial thrombosis. |
| Databáze: | OpenAIRE |
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