Chondroitin sulfate protects vascular endothelial cells from toxicities of extracellular histones

Fumihiko Nagano, Tomohiro Mizuno, Shuji Mizumoto, Kengo Yoshioka, Kazuo Takahashi, Naotake Tsuboi, Shoichi Maruyama, Shuhei Yamada, Tadashi Nagamatsu

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

Extracellular histones induce lethal thrombosis by promoting platelet aggregation, neutrophil migration, and cell injuries. Heparin, which has negative charges, can bind to extracellular histones; however, heparin strongly inhibits the activation of coagulation. Since chondroitin sulfate (CS) shows less effect on the coagulation system than heparin does, CS has the potential to become an effective drug for lethal thrombosis with high risk of bleeding. To elucidate the therapeutic mechanisms of CS in lethal thrombosis, we investigated the interaction between CS and extracellular histones. Mouse vascular endothelial cells were incubated with histones in the presence of heparin or CS, and the expression of caspase-3/7 was measured. The interactions between histones and heparin or CS were measured by surface plasmon resonance analysis. Vascular permeability, platelet counts, liver and renal functions, and coagulation times were evaluated in an in vivo assay. The apoptosis induced by histones was inhibited by treatment with heparin or CS. Heparin and CS showed strong binding to histones and inhibited vascular hyperpermeability. The platelet counts as well as liver and renal functions were not decreased by the treatment with heparin or CS. Moreover, CS showed less effect on the coagulation system than heparin did. These results suggested that CS can be a novel agent for lethal thrombosis with the risk for hemorrhage. Since vascular endothelial cell injuries occur at an early stage of lethal thrombosis, administration of CS might be a useful approach.

Original languageEnglish
Pages (from-to)48-55
Number of pages8
JournalEuropean Journal of Pharmacology
Volume826
DOIs
Publication statusPublished - 05-05-2018

Fingerprint

Chondroitin Sulfates
Histones
Endothelial Cells
Heparin
Thrombosis
Platelet Count
Hemorrhage
Caspase 7
Kidney
Surface Plasmon Resonance
Liver
Wounds and Injuries
Capillary Permeability
Platelet Aggregation
Caspase 3
Cell Movement
Blood Vessels
Neutrophils
Apoptosis

All Science Journal Classification (ASJC) codes

  • Pharmacology

Cite this

Nagano, Fumihiko ; Mizuno, Tomohiro ; Mizumoto, Shuji ; Yoshioka, Kengo ; Takahashi, Kazuo ; Tsuboi, Naotake ; Maruyama, Shoichi ; Yamada, Shuhei ; Nagamatsu, Tadashi. / Chondroitin sulfate protects vascular endothelial cells from toxicities of extracellular histones. In: European Journal of Pharmacology. 2018 ; Vol. 826. pp. 48-55.
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Nagano, F, Mizuno, T, Mizumoto, S, Yoshioka, K, Takahashi, K, Tsuboi, N, Maruyama, S, Yamada, S & Nagamatsu, T 2018, 'Chondroitin sulfate protects vascular endothelial cells from toxicities of extracellular histones', European Journal of Pharmacology, vol. 826, pp. 48-55. https://doi.org/10.1016/j.ejphar.2018.02.043

Chondroitin sulfate protects vascular endothelial cells from toxicities of extracellular histones. / Nagano, Fumihiko; Mizuno, Tomohiro; Mizumoto, Shuji; Yoshioka, Kengo; Takahashi, Kazuo; Tsuboi, Naotake; Maruyama, Shoichi; Yamada, Shuhei; Nagamatsu, Tadashi.

In: European Journal of Pharmacology, Vol. 826, 05.05.2018, p. 48-55.

Research output: Contribution to journalArticle

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AU - Nagano, Fumihiko

AU - Mizuno, Tomohiro

AU - Mizumoto, Shuji

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AU - Takahashi, Kazuo

AU - Tsuboi, Naotake

AU - Maruyama, Shoichi

AU - Yamada, Shuhei

AU - Nagamatsu, Tadashi

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