Skip to main content
Top
Published in: Inflammation 2/2022

01-04-2022 | Septicemia | Original Article

Unfractionated Heparin Attenuated Histone-Induced Pulmonary Syndecan-1 Degradation in Mice: a Preliminary Study on the Roles of Heparinase Pathway

Authors: Sifeng Fu, Sihan Yu, Yilin Zhao, Xiaochun Ma, Xu Li

Published in: Inflammation | Issue 2/2022

Login to get access

Abstract

Endothelial glycocalyx degradation is thought to facilitate the development of sepsis. Histone is a significant mediator in sepsis. Unfractionated heparin (UFH) possessed beneficial effects on sepsis. Thereby, this study aims to figure out whether histone can disrupt glycocalyx and to investigate the protective effect and mechanism of UFH. Male mice (C57BL/6, 8–10 weeks old, weighing 20–25 g) were randomly divided into five groups including control group, histone group, histone + UFH group, histone + heparinase (HPA) inhibitor group, and histone + UFH + HPA inhibitor group. The mice were treated with histone (50 mg/kg) via tail vein immediately after HPA (20 mg/kg) injection. UFH (400 U/kg) was injected 1h after histone administration. The other groups were injected with equal volume of sterile saline accordingly. UFH alleviated histone-induced lung injury and pulmonary edema. UFH inhibited histone-induced lung coagulation activation and inflammatory response. UFH treatment markedly inhibited pulmonary glycocalyx degradation by reducing the histone-induced decrease in the levels of lung syndecan-1 mRNA and protein. UFH downregulated histone-induced expression of HPA mRNA and protein, and thus alleviated glycocalyx degradation. UFH protects against histone-induced pulmonary glycocalyx injury partly by heparinase pathway.
Literature
12.
go back to reference Yang, Y., V. Macleod, H.Q. Miao, A. Theus, F.H. Zhan, J.D. Shaughnessy, J. Sawyer, et al. 2007. Heparanase enhances syndecan-1 shedding: a novel mechanism for stimulation of tumor growth and metastasis. The Journal of biological chemistry 282(18): 13326-13333. https://doi.org/10.1074/jbc.M611259200. Yang, Y., V. Macleod, H.Q. Miao, A. Theus, F.H. Zhan, J.D. Shaughnessy, J. Sawyer, et al. 2007. Heparanase enhances syndecan-1 shedding: a novel mechanism for stimulation of tumor growth and metastasis. The Journal of biological chemistry 282(18): 13326-13333. https://​doi.​org/​10.​1074/​jbc.​M611259200.
13.
15.
go back to reference Piotti, A., D. Novelli, J.M.T. Anna Meessen, D. Ferlicca, S. Coppolecchia, A. Marino, and G. Salati, et al. 2021. Endothelial damage in septic shock patients as evidenced by circulating syndecan-1 sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS. Critical care (London, England) 25(1): 113. https://doi.org/10.1186/s13054-021-03545-1. Piotti, A., D. Novelli, J.M.T. Anna Meessen, D. Ferlicca, S. Coppolecchia, A. Marino, and G. Salati, et al. 2021. Endothelial damage in septic shock patients as evidenced by circulating syndecan-1 sphingosine-1-phosphate and soluble VE-cadherin: a substudy of ALBIOS. Critical care (London, England) 25(1): 113. https://​doi.​org/​10.​1186/​s13054-021-03545-1.
22.
go back to reference Alhamdi, Y., M. Zi, S.T. Abrams, T. Liu, Su. Dunhao, I. Welters, T. Dutt, E.J. Cartwright, G. Wang, and C.H. Toh. 2016. Circulating Histone Concentrations Differentially Affect the Predominance of Left or Right Ventricular Dysfunction in Critical Illness. Critical care medicine 44(5): e278-e288. https://doi.org/10.1097/CCM.0000000000001413.CrossRef Alhamdi, Y., M. Zi, S.T. Abrams, T. Liu, Su. Dunhao, I. Welters, T. Dutt, E.J. Cartwright, G. Wang, and C.H. Toh. 2016. Circulating Histone Concentrations Differentially Affect the Predominance of Left or Right Ventricular Dysfunction in Critical Illness. Critical care medicine 44(5): e278-e288. https://​doi.​org/​10.​1097/​CCM.​0000000000001413​.CrossRef
23.
27.
38.
go back to reference Van den Berg, B.M., M. Nieuwdorp, E.S.G. Stroes, and H. Vink. 2006. Glycocalyx and endothelial (dys) function: from mice to men. Pharmacological Report 58 Suppl:75-80. Van den Berg, B.M., M. Nieuwdorp, E.S.G. Stroes, and H. Vink. 2006. Glycocalyx and endothelial (dys) function: from mice to men. Pharmacological Report 58 Suppl:75-80.
46.
go back to reference Zhao, C., Z.D. Zhang, X.J. Zhang, X. Li, R. Zhu, and X.C. Ma. 2009. Evaluation of clinical effects on low-dose heparin therapy for sepsis. Zhonghua nei ke za zhi [Chinese journal of internal medicine] 48: 566–569. Zhao, C., Z.D. Zhang, X.J. Zhang, X. Li, R. Zhu, and X.C. Ma. 2009. Evaluation of clinical effects on low-dose heparin therapy for sepsis. Zhonghua nei ke za zhi [Chinese journal of internal medicine] 48: 566–569.
47.
go back to reference Spiess, B.D. 2017. Heparin: Effects upon the Glycocalyx and Endothelial Cells. The Journal of extra-corporeal Technology 49(3): 192-197. Spiess, B.D. 2017. Heparin: Effects upon the Glycocalyx and Endothelial Cells. The Journal of extra-corporeal Technology 49(3): 192-197.
48.
go back to reference Wildhagen, K.C., P. García de Frutos, C.P. Reutelingsperger, R. Schrijver, C. Aresté, A. Ortega-Gómez, N.M. Deckers, H. Coenraad Hemker, O. Soehnlein, and G.A. Nicolaes. 2014. Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis. Blood 123(7): 1098-1101. https://doi.org/10.1182/blood-2013-07-514984.CrossRefPubMed Wildhagen, K.C., P. García de Frutos, C.P. Reutelingsperger, R. Schrijver, C. Aresté, A. Ortega-Gómez, N.M. Deckers, H. Coenraad Hemker, O. Soehnlein, and G.A. Nicolaes. 2014. Nonanticoagulant heparin prevents histone-mediated cytotoxicity in vitro and improves survival in sepsis. Blood 123(7): 1098-1101. https://​doi.​org/​10.​1182/​blood-2013-07-514984.CrossRefPubMed
Metadata
Title
Unfractionated Heparin Attenuated Histone-Induced Pulmonary Syndecan-1 Degradation in Mice: a Preliminary Study on the Roles of Heparinase Pathway
Authors
Sifeng Fu
Sihan Yu
Yilin Zhao
Xiaochun Ma
Xu Li
Publication date
01-04-2022
Publisher
Springer US
Published in
Inflammation / Issue 2/2022
Print ISSN: 0360-3997
Electronic ISSN: 1573-2576
DOI
https://doi.org/10.1007/s10753-021-01578-w

Other articles of this Issue 2/2022

Inflammation 2/2022 Go to the issue