Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice

Abstract 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 invest...

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Autores principales:	Hui Wang, Qian Wang, Kyle Kleiman, Chiao Guo, Daniel T. Eitzman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/f245dceee28f4925af6d13a8eacd439a
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spelling	oai:doaj.org-article:f245dceee28f4925af6d13a8eacd439a2021-12-02T15:05:47ZHematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice10.1038/s41598-017-01887-x2045-2322https://doaj.org/article/f245dceee28f4925af6d13a8eacd439a2017-05-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-01887-xhttps://doaj.org/toc/2045-2322Abstract 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.Hui WangQian WangKyle KleimanChiao GuoDaniel T. EitzmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-7 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hui Wang Qian Wang Kyle Kleiman Chiao Guo Daniel T. Eitzman Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice
description	Abstract 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.
format	article
author	Hui Wang Qian Wang Kyle Kleiman Chiao Guo Daniel T. Eitzman
author_facet	Hui Wang Qian Wang Kyle Kleiman Chiao Guo Daniel T. Eitzman
author_sort	Hui Wang
title	Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice
title_short	Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice
title_full	Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice
title_fullStr	Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice
title_full_unstemmed	Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice
title_sort	hematopoietic deficiency of mir-223 attenuates thrombosis in response to photochemical injury in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/f245dceee28f4925af6d13a8eacd439a
work_keys_str_mv	AT huiwang hematopoieticdeficiencyofmir223attenuatesthrombosisinresponsetophotochemicalinjuryinmice AT qianwang hematopoieticdeficiencyofmir223attenuatesthrombosisinresponsetophotochemicalinjuryinmice AT kylekleiman hematopoieticdeficiencyofmir223attenuatesthrombosisinresponsetophotochemicalinjuryinmice AT chiaoguo hematopoieticdeficiencyofmir223attenuatesthrombosisinresponsetophotochemicalinjuryinmice AT danielteitzman hematopoieticdeficiencyofmir223attenuatesthrombosisinresponsetophotochemicalinjuryinmice
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Hematopoietic Deficiency of miR-223 Attenuates Thrombosis in Response to Photochemical Injury in Mice

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