Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice

Abstract The effect of lipid lowering on the incidence of deep venous thrombosis (DVT) is controversial. The purpose of this study was to determine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency on development of DVT in mice. Pcsk9 deficient (pcsk9 −/−) and wild-type...

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Autores principales:	Hui Wang, Qian Wang, Jintao Wang, Chiao Guo, Kyle Kleiman, He Meng, Jason S. Knight, Daniel T. Eitzman
Formato:	article
Lenguaje:	EN
Publicado:	Nature Portfolio 2017
Materias:	Medicine R Science Q
Acceso en línea:	https://doaj.org/article/a1651225529d469ab56256b91b18919b
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spelling	oai:doaj.org-article:a1651225529d469ab56256b91b18919b2021-12-02T11:41:12ZProprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice10.1038/s41598-017-14307-x2045-2322https://doaj.org/article/a1651225529d469ab56256b91b18919b2017-10-01T00:00:00Zhttps://doi.org/10.1038/s41598-017-14307-xhttps://doaj.org/toc/2045-2322Abstract The effect of lipid lowering on the incidence of deep venous thrombosis (DVT) is controversial. The purpose of this study was to determine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency on development of DVT in mice. Pcsk9 deficient (pcsk9 −/−) and wild-type (WT) littermates underwent partial inferior vena cava (IVC) ligation to induce venous thrombosis. 48 hours following IVC ligation, IVC thrombosis was evident in 60% of WT mice and 25% of pcsk9 −/− mice (p < 0.05). Analysis of IVC thrombosis revealed greater thrombus weight, length, myeloid cell recruitment, and more neutrophil extracellular trap formation (NETs) in WT compared to pcsk9 −/− mice. Intravital microscopy performed two hours following partial IVC ligation revealed that leukocyte firm attachment was increased in WT mice compared to mice undergoing a sham operation, however leukocyte attachment was reduced in pcsk9 −/− mice compared to WT mice. In conclusion, deficiency of PCSK9 is associated with protection from venous thrombosis. This protection is associated with reduced leukocyte recruitment and NET formation at the site of thrombosis.Hui WangQian WangJintao WangChiao GuoKyle KleimanHe MengJason S. KnightDaniel T. EitzmanNature PortfolioarticleMedicineRScienceQENScientific Reports, Vol 7, Iss 1, Pp 1-8 (2017)
institution	DOAJ
collection	DOAJ
language	EN
topic	Medicine R Science Q
spellingShingle	Medicine R Science Q Hui Wang Qian Wang Jintao Wang Chiao Guo Kyle Kleiman He Meng Jason S. Knight Daniel T. Eitzman Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice
description	Abstract The effect of lipid lowering on the incidence of deep venous thrombosis (DVT) is controversial. The purpose of this study was to determine the effect of proprotein convertase subtilisin/kexin type 9 (PCSK9) deficiency on development of DVT in mice. Pcsk9 deficient (pcsk9 −/−) and wild-type (WT) littermates underwent partial inferior vena cava (IVC) ligation to induce venous thrombosis. 48 hours following IVC ligation, IVC thrombosis was evident in 60% of WT mice and 25% of pcsk9 −/− mice (p < 0.05). Analysis of IVC thrombosis revealed greater thrombus weight, length, myeloid cell recruitment, and more neutrophil extracellular trap formation (NETs) in WT compared to pcsk9 −/− mice. Intravital microscopy performed two hours following partial IVC ligation revealed that leukocyte firm attachment was increased in WT mice compared to mice undergoing a sham operation, however leukocyte attachment was reduced in pcsk9 −/− mice compared to WT mice. In conclusion, deficiency of PCSK9 is associated with protection from venous thrombosis. This protection is associated with reduced leukocyte recruitment and NET formation at the site of thrombosis.
format	article
author	Hui Wang Qian Wang Jintao Wang Chiao Guo Kyle Kleiman He Meng Jason S. Knight Daniel T. Eitzman
author_facet	Hui Wang Qian Wang Jintao Wang Chiao Guo Kyle Kleiman He Meng Jason S. Knight Daniel T. Eitzman
author_sort	Hui Wang
title	Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice
title_short	Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice
title_full	Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice
title_fullStr	Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice
title_full_unstemmed	Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice
title_sort	proprotein convertase subtilisin/kexin type 9 (pcsk9) deficiency is protective against venous thrombosis in mice
publisher	Nature Portfolio
publishDate	2017
url	https://doaj.org/article/a1651225529d469ab56256b91b18919b
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Proprotein convertase subtilisin/kexin type 9 (PCSK9) Deficiency is Protective Against Venous Thrombosis in Mice

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