The procoagulant molecule plasminogen activator inhibitor-1 is associated with injury severity and shock in patients with and without traumatic brain injury

Condron, Mary; Rowell, Susan; Dewey, Elizabeth; Anderson, Taylor N.; Lealiiee, Lelani; Farrell, David H.; Hinson, Holly E.

doi:10.1097/ta.0000000000002040

Cited by 18 publications

(18 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Platelet-endothelial adhesion molecule-1 (PECAM-1) is also secreted by BMVECs, is involved in the adhesion of neutrophils to the endothelium, and is inducing thrombus formation ( Carlos et al, 1997 ). Plasminogen activator inhibitor-1 (PAI-1), as the principal inhibitor of the activation of plasminogen and fibrinolysis, also increases the risks for coagulopathy after TBI ( Condron et al, 2018 ). The molecular regulation mechanisms of coagulation disorder after TBI has not been fully elucidated.…”

Section: Introductionmentioning

confidence: 99%

RETRACTED: Upregulation of C Terminus of Hsc70-Interacting Protein Attenuates Apoptosis and Procoagulant Activity and Facilitates Brain Repair After Traumatic Brain Injury

Chen

Yao

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

Traumatic brain injury (TBI) could highly induce coagulopathy through breaking the dynamic balance between coagulation and fibrinolysis systems, which may be a major contributor to the progressive secondary injury cascade that occurs after TBI. Phosphatase and tensin homolog deleted on chromosome 10 (PTEN) inhibition is reported to exert neuroprotection in TBI, making it a potential regulatory target involved in TBI-induced coagulation disorder. PTEN level is controlled in a major way by E3 ligase-mediated degradation through the ubiquitin-proteasome system. The C terminus of Hsc70-interacting protein (CHIP) has been shown to regulate proteasomal degradation and ubiquitination level of PTEN. In the present study, CHIP was overexpressed and knocked down in mouse brain microvascular endothelial cells (bEnd.3) and tissues during the early phase of TBI. In vitro cell proliferation, cell apoptosis, migration capacity, and invasion capacity were determined. The changes of procoagulant and apoptosis molecules after TBI were also detected as well as the micrangium density and blood-brain barrier permeability after in vivo TBI. In vitro results demonstrated that CHIP overexpression facilitated bEnd.3 cell proliferation, migration, and invasion and downregulated cell apoptosis and the expressions of procoagulant molecules through promoting PTEN ubiquitination in a simulated TBI model with stretch-induced injury treatment. In vivo experiments also demonstrated that CHIP overexpression suppressed post-TBI apoptosis and procoagulant protein expressions, as well as increased microvessel density, reduced hemorrhagic injury, and blood-brain barrier permeability. These findings suggested that the upregulation of CHIP may attenuate apoptosis and procoagulant activity, facilitate brain repair, and thus exerts neuroprotective effects in TBI.

show abstract

Section: Introductionmentioning

confidence: 99%

RETRACTED: Upregulation of C Terminus of Hsc70-Interacting Protein Attenuates Apoptosis and Procoagulant Activity and Facilitates Brain Repair After Traumatic Brain Injury

Chen

Yao

et al. 2020

Front. Neurosci.

View full text Add to dashboard Cite

show abstract

“…Plasminogen activator inhibitor-1 (PAI-1) is a pro-coagulant that is released by platelets and the endothelium in response to inflammation, damage, or ischemia and can be used as early marker for endothelial injury based on its inhibitory function of urokinase-like plasminogen activator (uPA) (38). Elevations of PAI-1 in bronchiolar lavage fluid is associated with experimentally-induced pulmonary fibrosis after thoracic radiation exposure (39) and in patients with lethal acute respiratory distress syndrome (40).…”

Section: Discussionmentioning

confidence: 99%

Defining the Inflammatory Microenvironment in the Human Cochlea by Perilymph Analysis: Toward Liquid Biopsy of the Cochlea

et al. 2019

View full text Add to dashboard Cite

The molecular pathomechanisms in the majority of patients suffering from acute or progressive sensorineural hearing loss cannot be determined yet. The size and the complex architecture of the cochlea make biopsy and in-depth histological analyses impossible without severe damage of the organ. Thus, histopathology correlated to inner disease is only possible after death. The establishment of a technique for perilymph sampling during cochlear implantation may enable a liquid biopsy and characterization of the cochlear microenvironment. Inflammatory processes may not only participate in disease onset and progression in the inner ear, but may also control performance of the implant. However, little is known about cytokines and chemokines in the human inner ear as predictive markers for cochlear implant performance. First attempts to use multiplex protein arrays for inflammatory markers were successful for the identification of cytokines, chemokines, and endothelial markers present in the human perilymph. Moreover, unsupervised cluster and principal component analyses were used to group patients by lead cytokines and to correlate certain proteins to clinical data. Endothelial and epithelial factors were detected at higher concentrations than typical pro-inflammatory cytokines such as TNF-a or IL-6. Significant differences in VEGF family members have been observed comparing patients with deafness to patients with residual hearing with significantly reduced VEGF-D levels in patients with deafness. In addition, there is a trend toward higher IGFBP-1 levels in these patients. Hence, endothelial and epithelial factors in combination with cytokines may present robust biomarker candidates and will be investigated in future studies in more detail. Thus, multiplex protein arrays are feasible in very small perilymph samples allowing a qualitative and quantitative analysis of inflammatory markers. More results are required to advance this method for elucidating the development and course of specific inner ear diseases or for perioperative characterization of cochlear implant patients.

show abstract

“…31 Further investigation into this phenotypic variation is warranted, as early treatment decisions, including the selective use of fibrinolytic inhibitors and activators, may be guided by phenotype. 30,32 Fibrinolytic disruption after TBI is complicated by several differences in biochemical and cellular function. Within the brain, synthesis and expression of fibrinolytic proteases occur both in vascular tissue and neuronal cells, where they serve several additional roles.…”

Section: Fibrinolysis In Traumatic Brain Injurymentioning

confidence: 99%

“…In a mouse model of TBI, elevated PAI-1 is associated with impaired fibrinolysis, microthrombi formation, and lesion expansion. 43 In human studies, PAI-1 exerts a procoagulant effect by inhibiting thrombomodulin and activated protein C. 32 In the context of trauma-related hyperfibrinolysis, upregulation of tPA, the primary protease responsible for the conversion of plasminogen to plasmin, results in complex formation with PAI-1 and a resultant decrease in the ratio of active (unbound) PAI-1 to complexed PAI-1. 11 Systemic posttraumatic release of endogenous tPA is thought to result from endothelial damage secondary to local tissue injury and ischemia, although similar levels of circulating tPA have been observed in patients with isolated TBI compared with those with extracranial traumatic injuries.…”

Section: Diagnostic Indicators Of Fibrinolysis Blood-based Biomarkersmentioning

confidence: 99%

Fibrinolysis in Traumatic Brain Injury: Diagnosis, Management, and Clinical Considerations

Anderson

Farrell

Rowell

2021

Semin Thromb Hemost

View full text Add to dashboard Cite

Posttraumatic coagulopathy involves disruption of both the coagulation and fibrinolytic pathways secondary to tissue damage, hypotension, and inflammatory upregulation. This phenomenon contributes to delayed complications after traumatic brain injury (TBI), including intracranial hemorrhage progression and systemic disseminated intravascular coagulopathy. Development of an early hyperfibrinolytic state may result in uncontrolled bleeding and is associated with increased mortality in patients with TBI. Although fibrinolytic assays are not routinely performed in the assessment of posttraumatic coagulopathy, circulating biomarkers such as D-dimer and fibrin degradation products have demonstrated potential utility in outcome prediction. Unfortunately, the relatively delayed nature of these tests limits their clinical utility. In contrast, viscoelastic tests are able to provide a rapid global assessment of coagulopathy, although their ability to reliably identify disruptions in the fibrinolytic cascade remains unclear. Limited evidence supports the use of hypertonic saline, cryoprecipitate, and plasma to correct fibrinolytic disruption; however, some studies suggest more harm than benefit. Recently, early use of tranexamic acid in patients with TBI and confirmed hyperfibrinolysis has been proposed as a strategy to further improve clinical outcomes. Moving forward, further delineation of TBI phenotypes and the clinical implications of fibrinolysis based on phenotypic variation is needed. In this review, we summarize the clinical aspects of fibrinolysis in TBI, including diagnosis, treatment, and clinical correlates, with identification of targeted areas for future research efforts.

show abstract

The procoagulant molecule plasminogen activator inhibitor-1 is associated with injury severity and shock in patients with and without traumatic brain injury

Abstract: Prognostic, level III.

Cited by 18 publications

References 22 publications

RETRACTED: Upregulation of C Terminus of Hsc70-Interacting Protein Attenuates Apoptosis and Procoagulant Activity and Facilitates Brain Repair After Traumatic Brain Injury

RETRACTED: Upregulation of C Terminus of Hsc70-Interacting Protein Attenuates Apoptosis and Procoagulant Activity and Facilitates Brain Repair After Traumatic Brain Injury

Defining the Inflammatory Microenvironment in the Human Cochlea by Perilymph Analysis: Toward Liquid Biopsy of the Cochlea

Fibrinolysis in Traumatic Brain Injury: Diagnosis, Management, and Clinical Considerations

Contact Info

Product

Resources

About