Cytokines, Adhesion Molecules, and Matrix Metalloproteases as Predisposing, Diagnostic, and Prognostic Factors in Venous Thrombosis

Mosevoll, Knut Anders; Johansen, Silje; Wendelbo, Øystein; Nepstad, Ina; Bruserud, Øystein; Reikvam, Håkon

doi:10.3389/fmed.2018.00147

Cited by 50 publications

(47 citation statements)

References 100 publications

(118 reference statements)

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“…The main pro-inflammatory cytokines belong to the IL-1 families, IL-6, TNF families, and MCP-1 [34,35]. These cytokines are initiators of the inflammatory response and promote the expression of adhesion molecules [36,37]. Our results support that these proinflammatory mediators upregulated adhesion molecules and worsened the outcome of stroke in CLEC14A-KO mice.…”

Section: Discussionsupporting

confidence: 75%

CLEC14A deficiency exacerbates neuronal loss by increasing blood-brain barrier permeability and inflammation

Kim

Lee

Zhang

et al. 2020

J Neuroinflammation

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Background: Ischemic stroke is a main cause of mortality. Blood-brain barrier (BBB) breakdown appears to play a critical role in inflammation in patients with ischemic stroke and acceleration of brain injury. The BBB has a protective function and is composed of endothelial cells, pericytes, and astrocytes. In ischemic stroke treatments, regulation of vascular endothelial growth factor (VEGF)-A and vascular endothelial growth factor receptor (VEGFR)-2 is a crucial target despite adverse effects. Our previous study found that loss of C-type lectin family 14 member A (CLEC14A) activated VEGF-A/VEGFR-2 signaling in developmental and tumoral angiogenesis. Here, we evaluate the effects of BBB impairment caused by CLEC14A deficiency in ischemia-reperfusion injury. Methods: In vitro fluorescein isothiocyanate (FITC)-dextran permeability, transendothelial electrical resistance (TEER) assay, and immunostaining were used to evaluate endothelial integrity. BBB permeability was assessed using Evans blue dye and FITC-dextran injection in Clec14a −/− (CLEC14A-KO) mice and wild-type mice. Middle cerebral artery occlusion surgery and behavioral assessments were performed to evaluate the neurologic damage. The change of tight junctional proteins, adhesion molecules, pro-inflammatory cytokines, and microglial were confirmed by immunofluorescence staining, Western blotting, and quantitative reverse transcription polymerase chain reaction of brain samples. Results: In endothelial cells, knockdown of CLEC14A increased FITC-dextran permeability and decreased transendothelial electrical resistance; the severity of this effect increased with VEGF treatment. Immunofluorescence staining revealed that tight junctional proteins were attenuated in the CLEC14A knockdown endothelial cells. Consistent with the in vitro results, CLEC14A-KO mice that were injected with Evans blue dye had cerebral vascular leakage at postnatal day 8; wild-type mice had no leakage. We used a middle cerebral artery occlusion model and found that CLEC14A-KO mice had severe infarcted brain and neurological deficits with upregulated VEGFR-2 expression. FITC-dextran leakage was present in CLEC14A-KO mice after ischemia-reperfusion, and the numbers of tight junctional molecules were significantly decreased. Loss of CLEC14A increased the pro-inflammatory response through adhesion molecule expression, and glial cells were activated. Conclusions: These results suggest that activation of VEGFR-2 in CLEC14A-KO mice aggravates ischemic stroke by exacerbating cerebral vascular leakage and increasing neuronal inflammation after ischemia-reperfusion injury.

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Section: Discussionsupporting

confidence: 75%

CLEC14A deficiency exacerbates neuronal loss by increasing blood-brain barrier permeability and inflammation

Kim

Lee

Zhang

et al. 2020

J Neuroinflammation

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“…Cytokines have the ability to interact with the hemostatic system via several pathways. The upregulation of tissue factor (TF), the main activator of coagulation in vivo, can be induced by pro-inflammatory cytokines (e.g., TNF-α, Il-1β, IL-6, IL-8) and inhibited by anti-inflammatory cytokines (e.g., IL-4, IL-10) [6,7,10,12,[29][30][31][32][33]. Furthermore, cytokines (e.g., IL-8) can trigger the release of so-called neutrophil extracellular traps (NETs) by neutrophils, which can promote the formation of a thrombus [11,12,[34][35][36].…”

Section: Discussionmentioning

confidence: 99%

Low Systemic Levels of Chemokine C-C Motif Ligand 3 (CCL3) are Associated with a High Risk of Venous Thromboembolism in Patients with Glioma

Nazari

Marosi

Moik

et al. 2019

Cancers

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A tight interplay between inflammation and hemostasis has been described as a potential driver for developing venous thromboembolism (VTE). Here, we investigated the association of systemic cytokine levels and risk of VTE in patients with glioma. This analysis was conducted within the prospective, observational Vienna Cancer and Thrombosis Study. Patients with glioma were included at time of diagnosis or progression and were observed for a maximum of two years. Primary endpoint was objectively confirmed VTE. At study entry, a single blood draw was performed. A panel of nine cytokines was measured in serum samples with the xMAP technology developed by Luminex. Results: Overall, 76 glioma patients were included in this analysis, and 10 (13.2%) of them developed VTE during the follow-up. Chemokine C-C motif ligand 3 (CCL3) levels were inversely associated with risk of VTE (hazard ratio [HR] per double increase, 95% confidence interval [CI]: 0.385, 95% CI: 0.161–0.925, p = 0.033), while there was no association between the risk of VTE and serum levels of interleukin (IL)-1β, IL-4, IL-6, IL-8, IL-10, IL-11, tumor necrosis factor (TNF)-α and vascular endothelial growth factor (VEGF), respectively. In conclusion, low serum levels of CCL3 were associated with an increased risk of VTE. CCL3 might serve as a potential biomarker to predict VTE risk in patients with glioma.

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“…151 Thrombosis is always important to be aware of, as malignancy is a main risk factor for the development of thrombosis. 152 Rheumatologic disorders are also associated with the clinical manifestations of a number of solid and hematological diseases and represent an important clue during the early diagnosis and treatment of the cancer diseases. 153 Conclusions.…”

Section: Different Local Resistance Patterns Require Adaptationsmentioning

confidence: 99%

Febrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment

Hansen¹,

Wendelbo²,

Bruserud³

et al. 2019

Mediterr J Hematol Infect Dis

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Acute leukemias are a group of aggressive malignant diseases associated with a high degree of morbidity and mortality. An important cause of both the latter is infectious complications. Patients with acute leukemia are highly susceptible to infectious diseases due to factors related to the disease itself, factors attributed to treatment, and specific individual risk factors in each patient. Patients with chemotherapy-induced neutropenia are at particularly high risk, and microbiological agents include viral, bacterial and fungal agents. The etiology is often unknown in infectious complications, although adequate patient evaluation and sampling have diagnostic, prognostic and treatment-related consequences. Bacterial infections include a wide range of potential microbes, both Gram-negative and Gram-positive species, while fungal infections include both mold and yeast. A recurring problem is increasing resistance to antimicrobial agents, and in particular, this applies to extended-spectrum beta-lactamase resistance (ESBL), Pseudomonas aeruginosa, methicillin-resistant Staphylococcus aureus (MRSA), vancomycin-resistant Enterococcus (VRE) and even carbapenemase-producing Enterobacteriaceae (CPE). International guidelines for the treatment of sepsis in leukemia patients include the use of broad-spectrum Pseudomonas-acting antibiotics. However, one should implant the knowledge of local microbiological epidemiology and resistance conditions in treatment decisions. Here, we discuss infectious diseases in acute leukemia with a major focus on febrile neutropenia and sepsis, and we problematize the diagnostic, prognostic, and therapeutic aspects of infectious complications in this patient group. Meticulously and thorough clinical and radiological examination combined with adequate microbiology samples are cornerstones of the examination. Diagnostic and prognostic evaluation includes patient review according to the multinational association for supportive care in cancer (MASCC) and sequential organ failure assessment (SOFA) scoring system. Antimicrobial treatments for important etiological agents are presented. The main challenge for reducing the spread of resistant microbes is to avoid unnecessary antibiotic treatment, but without giving to narrow treatment to the febrile neutropenic patient that reduce the prognosis.

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Cytokines, Adhesion Molecules, and Matrix Metalloproteases as Predisposing, Diagnostic, and Prognostic Factors in Venous Thrombosis

Cited by 50 publications

References 100 publications

CLEC14A deficiency exacerbates neuronal loss by increasing blood-brain barrier permeability and inflammation

CLEC14A deficiency exacerbates neuronal loss by increasing blood-brain barrier permeability and inflammation

Low Systemic Levels of Chemokine C-C Motif Ligand 3 (CCL3) are Associated with a High Risk of Venous Thromboembolism in Patients with Glioma

Febrile Neutropenia in Acute Leukemia. Epidemiology, Etiology, Pathophysiology and Treatment

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