Effects of antithrombin III treatment in vascular injury model of mice

Maeda, Akiko; Ohta, Kunio; Ohta, Kazuhide; Nakayama, Yuko; Hashida, Yoko; Toma, Tomoko; Saito, Tatsuhito; Maruhashi, Keiko; Yachie, Akihiro

doi:10.1111/j.1442-200x.2011.03350.x

Cited by 5 publications

(7 citation statements)

References 24 publications

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“…Studies have previously reported that the occurrence and development of certain cancers was also closely associated with SERPINC1; Zietek et al (22,23) reported increased levels of ATIII in the serum of patients with kidney cancer and the tumor tissues of patients with bladder cancer. Other studies observed that SERPINC1-encoded proteins exhibited inhibitory effects on angiogenesis and suppressed proliferation (24,25). To the best of our knowledge, the role of SERPINC1 in the occurrence and development of NPC has not been investigated.…”

Section: Introductionmentioning

confidence: 93%

Knockdown of serpin peptidase inhibitor clade C member�1 inhibits the growth of nasopharyngeal carcinoma cells

Yin

Xiong

et al. 2019

Mol Med Report

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Nasopharyngeal carcinoma (NPC) is a type of cancer originating in the nasopharynx. There are no NPC-specific treatments available at present. Serpin peptidase inhibitor clade C member 1 (SERPINC1) serves roles in anticoagulation and anti-inflammation. The aim of the present study was to investigate the role of SERPINC1 in the proliferation and apoptosis of NPC cells. Tumor and adjacent healthy tissue samples were collected from patients with NPC. Additionally, the SERPINC1 gene was silenced in the HNE3 cell line using short interfering RNA targeted against SERPINC1 (SERPINC1-siRNA). Cell viability was determined via a Cell Counting Kit-8 assay; furthermore, proliferation and apoptosis were investigated via flow cytometry. Western blotting and reverse transcription-quantitative polymerase chain reaction analysis were performed to determine the expression levels of protein and mRNA. It was revealed that the expression levels of SERPINC1 mRNA and protein were increased in NPC tumor tissues compared with in adjacent healthy tissues. The expression of SERPINC1 mRNA and protein in HNE3 cells decreased following SERPINC1-siRNA transfection. Furthermore, knockdown of SERPINC1 promoted apoptosis and inhibited proliferation. It was also demonstrated that silencing SERPINC1 upregulated the expression of B-cell lymphoma-2 (Bcl-2)-associated X protein and p53 mRNA and protein, and downregulated that of Bcl-2, survivin and cyclin D1. Downregulation of SERPINC1 reduced the phosphorylation of phosphatidylinositol 3-kinase (PI3K), protein kinase B (Akt) and mammalian target of rapamycin (mTOR). Thus, SERPINC1 knockdown may promote the apoptosis of HNE3 cells and inhibit proliferation via the suppression of the PI3K/Akt/mTOR signaling pathway.

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Section: Introductionmentioning

confidence: 93%

Knockdown of serpin peptidase inhibitor clade C member�1 inhibits the growth of nasopharyngeal carcinoma cells

Yin

Xiong

et al. 2019

Mol Med Report

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“…It inhibits thrombin and other serine proteases generated by the coagulation cascade. High-dose ATIII has been shown to have a strong anti-inflammatory effect in mouse models of endothelial damage, such as DIC and I/R injury [60]. …”

Section: Atiii As a Potential Treatment For Kidney-related Diseasesmentioning

confidence: 99%

“…ATIII can not only inactivate thrombin and other serine proteases in the coagulation cascade, but also suppress the inflammatory response of the immune system [67,68]. Maeda et al [60] showed that high-dose ATIII alters the consequences of vascular injury by reducing mural thrombus formation and limiting the inflammatory reaction of the vessel wall, without exerting a prolonged inhibitory effect on positive vascular remodeling. The treatment with ATIII reduces inflammatory cell infiltration, as determined by the CD11b + cell density in the adventitial area.…”

Section: Atiii As a Potential Treatment For Kidney-related Diseasesmentioning

confidence: 99%

“…The treatment with ATIII reduces inflammatory cell infiltration, as determined by the CD11b + cell density in the adventitial area. Appropriate use of ATIII in patients with acute vascular injury or undergoing procedures that have a risk of vascular endothelial injury will result in rapid and effective repair of the damaged vessels [60]. According to other studies about renal I/R injury, the coagulation system is activated 2 h after injury and the activity of coagulation reaches a peak at 12 h [69].…”

Section: Atiii As a Potential Treatment For Kidney-related Diseasesmentioning

confidence: 99%

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SerpinC1/Antithrombin III in kidney-related diseases

Wang

Liang

2017

Clinical Science

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The gene SerpinC1 encodes a serine protease inhibitor named antithrombin III (ATIII). This protease demonstrates both anticoagulant and anti-inflammatory action. ATIII is the most important coagulation factor inhibitor, and even minor changes in ATIII can significantly alter the risk of thromboembolism. ATIII can also suppress inflammation via a coagulation-dependent or -independent effect. Moreover, apart from ATIII deficiency, ATIII and its gene SerpinC1 may also be related to many diseases (e.g. hypertension, kidney diseases). The present review summarizes how ATIII affects the progress of kidney disease and its mechanism. Further studies are required to investigate how ATIII affects renal function and the treatment.

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“…11 Antithrombin alters microvasculature cellular interactions and improves recovery from tissue injury in animal models of ischemia-reperfusion, acute lung injury, and sepsis. [12][13][14][15][16] Indeed, post-TBI AT-III therapy reduces in vivo penumbral neurovasculature recruitment of circulating leucocytes while mitigating both local microvascular permeability and cerebral edema. 11 While this work offers the promise of acute functional recovery in injured animals, it is unknown if AT-III affects post-TBI cognitive recovery weeks after injury.…”

mentioning

confidence: 99%

Post-traumatic brain injury antithrombin III recovers Morris water maze cognitive performance, improving cued and spatial learning

ElSaadani

Ahmed

Jacovides

et al. 2021

J Trauma Acute Care Surg

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BACKGROUND:Neuroinflammation and cerebral edema development following severe traumatic brain injury (TBI) affect subsequent cognitive recovery. Independent of its anticoagulant effects, antithrombin III (AT-III) has been shown to block neurovascular inflammation after severe TBI, reduce cerebral endothelial-leukocyte interactions, and decrease blood-brain barrier permeability. We hypothesized that AT-III administration after TBI would improve post-TBI cognitive recovery, specifically enhancing learning, and memory. METHODS:Fifteen CD1 male mice were randomized to undergo severe TBI (controlled cortical impact [CCI]: velocity, 6 m/s; depth, 1 mm; diameter, 3 mm) or sham craniotomy and received either intravenous AT-III (250 IU/kg) or vehicle (VEH/saline) 15 minutes and 24 hours post-TBI. Animals underwent Morris water maze testing from 6 to 14 days postinjury consisting of cued learning trials (platform visible), spatial learning trials (platform invisible, spatial cues present), and probe (memory) trials (platform removed, spatial cues present). Intergroup differences were assessed by the Kruskal-Wallis test (p < 0.05). RESULTS:Morris water maze testing demonstrated that cumulative cued learning (overall mean time in seconds to reach the platform on days 6-8) was worst in CCI-VEH animals (26.1 ± 2.4 seconds) compared with CCI-AT-III counterparts (20.3 ± 2.1 seconds, p < 0.01).Cumulative noncued spatial learning was also worst in the CCI-VEH group (23.4 ± 1.8 seconds) but improved with AT-III (17.6 ± 1.5 seconds, p < 0.01). In probe trials, AT-III failed to significantly improve memory ability. Animals that underwent sham craniotomy demonstrated preserved learning and memory compared with all CCI counterparts (p < 0.05). CONCLUSION:Antithrombin III improves neurocognitive recovery weeks after TBI. This improvement is particularly related to improvement in learning but not memory function. Pharmacologic support of enhanced learning may support new skill acquisition or relearning to improve outcomes after TBI.

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Effects of antithrombin III treatment in vascular injury model of mice

Abstract: Our results suggested that a high dose of ATIII may influence the sequelae of arterial injury by reducing mural thrombus formation and limiting the inflammatory reaction of the vessel wall without altering the process of vascular remodeling.

Cited by 5 publications

References 24 publications

Knockdown of serpin peptidase inhibitor clade C member�1 inhibits the growth of nasopharyngeal carcinoma cells

Knockdown of serpin peptidase inhibitor clade C member�1 inhibits the growth of nasopharyngeal carcinoma cells

SerpinC1/Antithrombin III in kidney-related diseases

Post-traumatic brain injury antithrombin III recovers Morris water maze cognitive performance, improving cued and spatial learning

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