Circulating syndecan-1 predicts the development of disseminated intravascular coagulation in patients with sepsis

Ikeda, Mitsunori; Matsumoto, Hisatake; Ogura, Hiroshi; Hirose, Tomoya; Shimizu, Kentaro; Yamamoto, Keiji; Maruyama, Ikuro

doi:10.1016/j.jcrc.2017.07.049

Cited by 74 publications

(85 citation statements)

References 35 publications

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“…Chappell et al (34) indicated that protection of the endothelial glycocalyx decreased platelet adhesion in an ischemia/reperfusion pig model. Ikeda et al (35) revealed that SDC-1 HPA, heparanase; HS, heparan sulfate; SDC-1, syndecan-1; TNF-α, tumor necrosis factor-α; IL-6, interleukin-6; F1+2, prothrombin fragment 1+2; TAT, thrombin-antithrombin complex; AT, antithrombin; PAI-1, plasminogen activator inhibitor-1. Correlations between HPA, HS, SDC-1 and TNF-α, IL-6, F1+2, TAT, AT-III and PAI-1 were assessed by using the Spearman rank test.…”

Section: Discussionmentioning

confidence: 99%

Both UFH and NAH alleviate shedding of endothelial glycocalyx and coagulopathy in LPS‑induced sepsis

et al. 2019

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Sepsis commonly progresses to disseminated intravascular coagulation and induces the activation of heparanase (HPA) and the shedding of endothelial glycocalyx constituents, including syndecan-1 (SDC-1) and heparan sulphate (HS). However, the degradation of glycocalyx and its association with coagulation disorders remains undetermined. The present study aimed to evaluate the effect of unfractionated heparin (UFH) and N-acetylheparin (NAH), which is a non-anticoagulant heparin derivative, on endothelial glycocalyx and coagulation function in a lipopolysaccharide (LPS)-induced sepsis rat model, and to compare the differences observed in coagulation function between UFH and NAH. Experimental rats were randomly assigned to four groups: Control; LPS; UFH + LPS; and NAH + LPS. Rats were administered UFH or NAH and subsequently, ~1 min later, administered LPS (10 mg/kg; intravenous). The blood and lung tissues of rats were collected 0.5, 2 and 6 h after LPS injection, and were used for subsequent analysis. The results demonstrated that HPA activity and SDC-1 and HS levels increased, and this increase was associated with inflammatory cytokines and coagulation/fibrinolysis markers in the sepsis rat model. Histopathological examination was performed, and the lung injury score and lung wet/dry ratio indicated that UFH and NAH also significantly improved lung tissue injury. The results of the ELISA analysis demonstrated that UFH and NAH treatment: i) significantly decreased the levels of inflammatory cytokines including tumor necrosis factor-α and interleukin-6; ii) inhibited HPA activity and protected the integrity of the glycocalyx, which was identified by decreased HS and SDC-1 levels; and iii) decreased the levels of prothrombin fragment 1+2, thrombin-antithrombin complex, and plasminogen activator inhibitor-1 and increased the levels of fibrinogen and antithrombin-III. Preconditioning with UFH decreased the plasma activated partial thromboplastin time. These results indicated that UFH and NAH may alleviate sepsis-induced coagulopathy, and this effect may have been due to an inhibition of HPA activity and decrease in the shedding of the endothelial glycocalyx.

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Section: Discussionmentioning

confidence: 99%

Both UFH and NAH alleviate shedding of endothelial glycocalyx and coagulopathy in LPS‑induced sepsis

et al. 2019

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“…Ikeda et al . reported that syndecan‐1 levels were associated with not only the severity of sepsis but also the development of DIC.…”

Section: Structure and Functionmentioning

confidence: 99%

“…Typically, the excessive activation of coagulation leads to disseminated intravascular coagulation (DIC), and the disruption of the glycocalyx contributes to this status. Ikeda et al [27] reported that syndecan-1 levels were associated with not only the severity of sepsis but also the development of DIC.…”

Section: Maintenance Of Anticoagulationmentioning

confidence: 99%

Derangement of the endothelial glycocalyx in sepsis

Iba

Levy

2019

Journal of Thrombosis and Haemostasis

237

296

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Summary The vascular endothelial surface is coated by the glycocalyx, a ubiquitous gel‐like layer composed of a membrane‐binding domain that contains proteoglycans, glycosaminoglycan side‐chains, and plasma proteins such as albumin and antithrombin. The endothelial glycocalyx plays a critical role in maintaining vascular homeostasis. However, this component is highly vulnerable to damage and is also difficult to examine. Recent advances in analytical techniques have enabled biochemical, visual and computational investigation of this vascular component. The glycocalyx modulates leukocyte–endothelial interactions, thrombus formation and other processes that lead to microcirculatory dysfunction and critical organ injury in sepsis. It also acts as a regulator of vascular permeability and contains mechanosensors as well as receptors for growth factors and anticoagulants. During the initial onset of sepsis, the glycocalyx is damaged and circulating levels of glycocalyx components, including syndecans, heparan sulfate and hyaluronic acid, can be measured and are reportedly useful as biomarkers for sepsis. Also, a new methodology using side‐stream dark‐field imaging is now clinically available for assessing the glycocalyx. Multiple factors including hypervolemia and hyperglycemia are toxic to the glycocalyx, and several agents have been proposed as therapeutic modalities, although no single treatment has been proven to be clinically effective. In this article, we review the derangement of the glycocalyx in sepsis. Despite the accumulated knowledge regarding the important roles of the glycocalyx, the relationship between derangement of the endothelial glycocalyx and severity of sepsis or disseminated intravascular coagulation has not been adequately elucidated and further work is needed.

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“…Además, Maximilian Holzmann, y Martin Winkler (2018) [22]. Incluyen 55 pacientes de cirugía abdominal mayor 24 con cirugía oncológica electiva y 31 duodectomia pancreática, 22% desarrollaron sepsis, el 11% murieron (todos con choque refractario y disfunción multiorganica).…”

Section: Sindecano -1unclassified

“…Kaplan Meyer sobrevida con altos y bajos niveles de Sindecano -1 y Curvas ROC de Sindecano -1 como predictor de sepsis, y mortalidad a los 25 días [22] Lo mencionado en el estudio anterior se corrobora con otro estudio reciente realizado por Mitsunori Ikeda, Hisatake Matsumoto (2018), [23] niveles altos de sindecano -1 el primer día se correlacionan con mayor mortalidad a los 28 días con un AUROC de 0.85, y mayor gravedad (SOFA y APACHE).…”

Section: Figuraunclassified

Rol del glicocálix en la Sepsis: Revisión de La literatura y enfoque traslacional

Montero¹,

Páez

Villagómez³

et al. 2019

prosciences

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El endotelio vascular está cubierto por glicocálix en su región apical; una estructura compleja de macromoléculas formada por proteoglicanos y glicosaminoglicanos. Alteraciones en la fisiología de esta estructura en la sepsis podrían explicar la permeabilidad endotelial, vasoplejía, el estado procoagulante y la inflamación persistente; que clínicamente se ven asociados a disfunción de los órganos y consecuentemente alta mortalidad. Por lo que productos de la degradación del glicocálix podrían usarse como biomarcadores para diagnóstico y pronóstico. Además de convertirse en objetivos farmacológicos o guías de reanimación temprana, por lo que el conocimiento de los mecanismos moleculares involucrados es de vital importanciaen la práctica clínica.

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Circulating syndecan-1 predicts the development of disseminated intravascular coagulation in patients with sepsis

Cited by 74 publications

References 35 publications

Both UFH and NAH alleviate shedding of endothelial glycocalyx and coagulopathy in LPS‑induced sepsis

Both UFH and NAH alleviate shedding of endothelial glycocalyx and coagulopathy in LPS‑induced sepsis

Derangement of the endothelial glycocalyx in sepsis

Rol del glicocálix en la Sepsis: Revisión de La literatura y enfoque traslacional

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