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Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis

Iba, Toshiaki ; Levy, Jerrold H ; Aihara, Koichiro ; Kadota, Katsuhiko ; Tanaka, Hiroshi ; Sato, Koichi ; Nagaoka, Isao

International journal of molecular sciences, 2020-12, Vol.22 (1), p.176 [Periódico revisado por pares]

Switzerland: MDPI AG

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  • Título:
    Newly Developed Recombinant Antithrombin Protects the Endothelial Glycocalyx in an Endotoxin-Induced Rat Model of Sepsis
  • Autor: Iba, Toshiaki ; Levy, Jerrold H ; Aihara, Koichiro ; Kadota, Katsuhiko ; Tanaka, Hiroshi ; Sato, Koichi ; Nagaoka, Isao
  • Assuntos: Adhesion ; Albumins ; Animal models ; Animals ; Anticoagulants ; Antithrombin ; Biomarkers ; Blood ; Blood flow ; Coagulation ; Endothelium ; Endotoxins ; Evaluation ; glycocalyx ; Heparan sulfate ; hyaluronan ; Hyaluronic acid ; Ischemia ; Laboratories ; Lactic acid ; Leukocytes ; Microvasculature ; Perfusion ; Plasma ; Sepsis ; Software ; Syndecan ; syndecan-1
  • É parte de: International journal of molecular sciences, 2020-12, Vol.22 (1), p.176
  • Notas: ObjectType-Article-1
    SourceType-Scholarly Journals-1
    ObjectType-Feature-2
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  • Descrição: (1) Background: The endothelial glycocalyx is a primary target during the early phase of sepsis. We previously reported a newly developed recombinant non-fucosylated antithrombin has protective effects in vitro. We further evaluated the effects of this recombinant antithrombin on the glycocalyx damage in an animal model of sepsis. (2) Methods: Following endotoxin injection, in Wistar rats, circulating levels of hyaluronan, syndecan-1 and other biomarkers were evaluated in low-dose or high-dose recombinant antithrombin-treated animals and a control group ( = 7 per group). Leukocyte adhesion and blood flow were evaluated with intravital microscopy. The glycocalyx was also examined using side-stream dark-field imaging. (3) Results: The activation of coagulation was inhibited by recombinant antithrombin, leukocyte adhesion was significantly decreased, and flow was better maintained in the high-dose group (both < 0.05). Circulating levels of syndecan-1 ( < 0.01, high-dose group) and hyaluronan ( < 0.05, low-dose group; < 0.01, high-dose group) were significantly reduced by recombinant antithrombin treatment. Increases in lactate and decreases in albumin levels were significantly attenuated in the high-dose group ( < 0.05, respectively). The glycocalyx thickness was reduced over time in control animals, but the derangement was attenuated and microvascular perfusion was better maintained in the high-dose group recombinant antithrombin group ( < 0.05). (4) Conclusions: Recombinant antithrombin maintained vascular integrity and the microcirculation by preserving the glycocalyx in this sepsis model, effects that were more prominent with high-dose therapy.
  • Editor: Switzerland: MDPI AG
  • Idioma: Inglês
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  • Realização: ABCD-USP USP   Logos de Redes Sociais: Freepik

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