An evaluation of the ability of thrombospondin-1 to predict stroke outcomes and mortality after ischemic stroke

Qawasmeh, Majdi Al; Alhusban, Ahmed; Alfwaress, Firas

doi:10.1080/00207454.2020.1825417

Cited by 3 publications

(4 citation statements)

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“…THBS1 is known to be involved in inflammatory processes and thrombosis but also in a variety of other mechanisms including cell-cell interaction, and in wound healing [119]. Because of its multipotent character, studies on the role of THBS1 in human ischaemic stroke have been inconclusive when trying to define a precise role within the contribution to thrombosis [119][120][121]. The potential contribution of MMP9 and THBS1 (dys-)regulation to thrombosis, ischaemia and haemorrhagic infarction leading to EHM/abortion remains speculative but may be worth investigating by further research.…”

Section: Discussionmentioning

confidence: 99%

Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses

Giessler,

Goehring,

Jacob

et al. 2024

Journal of General Virology

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Herpesviruses establish a well-adapted balance with their host’s immune system. Despite this co-evolutionary balance, infections can lead to severe disease including neurological disorders in their natural host. In horses, equine herpesvirus 1 (EHV-1) causes respiratory disease, abortions, neonatal foal death and myeloencephalopathy (EHM) in ~10 % of acute infections worldwide. Many aspects of EHM pathogenesis and protection from EHM are still poorly understood. However, it has been shown that the incidence of EHM increases to >70 % in female horses >20 years of age. In this study we used old mares as an experimental equine EHV-1 model of EHM to identify host-specific factors contributing to EHM. Following experimental infection with the neuropathogenic strain EHV-1 Ab4, old mares and yearling horses were studied for 21 days post-infection. Nasal viral shedding and cell-associated viremia were assessed by quantitative PCR. Cytokine/chemokine responses were evaluated in nasal secretions and cerebrospinal fluid (CSF) by Luminex assay and in whole blood by quantitative real-time PCR. EHV-1-specific IgG sub-isotype responses were measured by ELISA. All young horses developed respiratory disease and a bi-phasic fever post-infection, but only 1/9 horses exhibited ataxia. In contrast, respiratory disease was absent in old mares, but all old mares developed EHM that resulted in euthanasia in 6/9 old mares. Old mares also presented significantly decreased nasal viral shedding but higher viremia coinciding with a single fever peak at the onset of viremia. According to clinical disease manifestation, horses were sorted into an EHM group (nine old horses and one young horse) and a non-EHM group (eight young horses) for assessment of host immune responses. Non-EHM horses showed an early upregulation of IFN-α (nasal secretions), IRF7/IRF9, IL-1β, CXCL10 and TBET (blood) in addition to an IFN-γ upregulation during viremia (blood). In contrast, IFN-α levels in nasal secretions of EHM horses were low and peak levels of IRF7, IRF9, CXCL10 and TGF-β (blood) coincided with viremia. Moreover, EHM horses showed significantly higher IL-10 levels in nasal secretions, peripheral blood mononuclear cells and CSF and higher serum IgG3/5 antibody titres compared to non-EHM horses. These results suggest that protection from EHM depends on timely induction of type 1 IFN and upregulation cytokines and chemokines that are representative of cellular immunity. In contrast, induction of regulatory or TH-2 type immunity appeared to correlate with an increased risk for EHM. It is likely that future vaccine development for protection from EHM must target shifting this ‘at-risk’ immunophenotype.

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Section: Discussionmentioning

confidence: 99%

Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses

Giessler,

Goehring,

Jacob

et al. 2024

Journal of General Virology

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“…There are also studies on non-routine laboratory projects, including CCL11 [ 31 ], plasma copeptin [ 32 ], plasma Klotho [ 33 ], plasma RGM-A [ 34 ], plasma TAFI [ 35 ], plasma copeptin [ 32 ], serum irisin [ 36 ], serum Tau protein [ 37 ], serum tight-junction protein [ 38 ], serum retinoic acid [ 39 ], thrombospondin-1 [ 40 ], remnant lipoproteins [ 41 ], and Lipocalin-2 [ 42 ]. However, these non-routine laboratory tests face limitations in clinical application due to the difficulty in detection.…”

Section: Discussionmentioning

confidence: 99%

Construction and comparison of short-term prognosis prediction model based on machine learning in acute ischemic stroke

Xing,

Jin,

Liu

2024

Heliyon

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“…Della-Morte et al (2012) observed that variation in the von Willebrand factor (VWF), THBS1, and SERPINE1 genes may involve in the pathogenesis of atherosclerotic plaque and that suggested THBS1 had the ability to interact with VWF, to be an candidate gene for arterial thrombosis (Bonnefoy et al, 2006). Nonetheless, no strong evidence supported the role of THBS1 in the occurrence of arterial thrombosis (van Schie et al, 2011), and the correlation between peripheral THBS1 levels and long-term outcome of IS (Gao et al, 2015;Al Qawasmeh et al, 2020) merely displayed a concomitant effect rather than sequential relationship of causality. Therefore, the causal relationship between THBS1 and IS was still lack of sufficient evidence.…”

Section: Discussionmentioning

confidence: 99%

“…Additionally, plasma THBS1 level elevated in patients with IS compared to the controls (Gao et al, 2015) as well as at 2h after tPA-treatment (Navarro-Sobrino et al, 2011). Thus, the serum THBS1 level was proposed to be an independent predictor of favorable outcome at baseline and after 6 months (Gao et al, 2015;Al Qawasmeh et al, 2020). Therefore, further population-based studies would be warranted to validate the association between THBS1 and IS.…”

Section: Introductionmentioning

confidence: 99%

Association of THBS1 genetic variants and mRNA expression with the risks of ischemic stroke and long-term death after stroke

Chen

Yang

et al. 2022

Front. Aging Neurosci.

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BackgroundThrombospondin-1 (THBS1) derived from platelets and acted as a critical mediator of hemostasis promoting platelet activation in thrombus formation. The biological connection of genetic variants and mRNA expression of THBS1 with ischemic stroke (IS) warrants further validation with population-based evidence.ObjectiveTo evaluate the association of single nucleotide polymorphisms (SNPs) and mRNA expression of THBS1 with the risks of IS and long-term death after stroke.MethodsA case-control study consisted of 4,584 IS patients recruited from five hospitals in Jiangsu, China, and 4,663 age-gender-matched controls free of IS. A cohort study enrolled 4,098 participants free of stroke and lasted from 2009 to 2022. Early collected 3158 IS patients aged between 35 and 80 years were followed up an average of 5.86-year to follow up their long-term death outcomes. Two tagSNPs of the THBS1 gene, rs2236471 and rs3743125, were genotyped in all subjects and THBS1 mRNA expression of peripheral leukocyte was measured using RT-qPCR in 314 IS cases and 314 controls.ResultsThere is no significant difference in genotype and haplotype frequencies of rs2236741 and rs3743125 between IS cases and controls (all P > 0.05). Furthermore, the cohort studies did not observe significant associations between THBS1 variants and the risk of IS incidence or long-term death after IS (all P > 0.05). The THBS1 mRNA expression level (2–ΔΔCT) in IS cases was approximately equal to that in controls (1.01 vs. 0.99, P = 0.833). In addition, THBS1 mRNA expression had no significant association with all-cause death, stroke death, and IS death of IS patients (all P > 0.05).ConclusionTherefore, our study suggested that there is no significant association of THBS1 polymorphisms and mRNA expression level with the risk of IS and long-term death after IS.

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An evaluation of the ability of thrombospondin-1 to predict stroke outcomes and mortality after ischemic stroke

Cited by 3 publications

References 10 publications

Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses

Impact of the host immune response on the development of equine herpesvirus myeloencephalopathy in horses

Construction and comparison of short-term prognosis prediction model based on machine learning in acute ischemic stroke

Association of THBS1 genetic variants and mRNA expression with the risks of ischemic stroke and long-term death after stroke

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