P-Selectin Blockade in the Treatment of Painful Vaso-Occlusive Crises in Sickle Cell Disease: A Spotlight on Crizanlizumab

Karki, Nabin Raj; Kutlar, Abdullah

doi:10.2147/jpr.s278285

Cited by 20 publications

(12 citation statements)

References 54 publications

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“…Endothelial cells in Sickle Cell Disease (SCD) express P-selectin on a long-term basis [ 11 ]. P-selectin upregulation in endothelial cells and platelets contributes to cell–cell interactions implicated in the development of vaso-occlusion and sickle cell pain crises [ 12 ]. P-selectin levels in the blood have been found to be elevated in a variety of acute and chronic cardiovascular diseases, including peripheral arterial disease, coronary artery disease, hypertension, and acute myocardial infarction [ 13 , 14 , 15 , 16 , 17 ].…”

Section: P-selectin In Human Diseasesmentioning

confidence: 99%

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

Agrati

Sacchi

Tartaglia

et al. 2021

IJMS

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In severe COVID-19, which is characterized by blood clots and neutrophil-platelet aggregates in the circulating blood and different tissues, an increased incidence of cardiovascular complications and venous thrombotic events has been reported. The inflammatory storm that characterizes severe infections may act as a driver capable of profoundly disrupting the complex interplay between platelets, endothelium, and leukocytes, thus contributing to the definition of COVID-19-associated coagulopathy. In this frame, P-selectin represents a key molecule expressed on endothelial cells and on activated platelets, and contributes to endothelial activation, leucocyte recruitment, rolling, and tissue migration. Briefly, we describe the current state of knowledge about P-selectin involvement in COVID-19 pathogenesis, its possible use as a severity marker and as a target for host-directed therapeutic intervention.

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Section: P-selectin In Human Diseasesmentioning

confidence: 99%

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

Agrati

Sacchi

Tartaglia

et al. 2021

IJMS

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“…This line of research could result in novel platelet-based (e.g. P-selectin blocking agents [32]) interventions for the prevention and treatment of MetS-related cognitive impairment.…”

Section: Discussion/conclusionmentioning

confidence: 99%

Is platelet activation a link between metabolic syndrome and cognitive impairment in patients with schizophrenia?

Okusaga

Vijayan

Rumbaut

2023

Preprint

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Introduction: Schizophrenia is a severe psychiatric condition associated with cognitive impairment and premature dementia. Furthermore, metabolic syndrome (MetS)-combined central obesity, diabetes, dyslipidemia and hypertension-is highly prevalent in patients with schizophrenia and is believed to contribute to cognitive impairment and premature dementia in patients with schizophrenia. However, the mechanisms by which MetS contributes to cognitive impairment in patients with schizophrenia is unclear. Based on the association of MetS with platelet activation and the ability of activated platelets to impact blood-brain-barrier function, we tested the hypothesis that platelet activation is associated with both MetS and cognitive impairment in two independent pilot samples of patients with schizophrenia. Methods: In the first pilot sample (sample A) we recruited 13 veterans with either schizophrenia or schizoaffective disorder with MetS (MetS+, n=6), and without MetS (MetS-, n=7). We administered the Measurement and Treatment Research to Improve Cognition in Schizophrenia (MATRICS) Consensus Cognitive Battery (MCCB) on all 13 veterans and assessed platelet activation using flow cytometry. In the second pilot sample (sample B), we identified 10 non-veteran MetS+ patients with schizophrenia and 10 age-, and sex-matched MetS- patients with schizophrenia from previously collected data on 106 patients enrolled in a non-MetS study. Participants in sample B had data on the NIH Toolbox cognitive battery (NIH Toolbox) and plasma soluble P-selectin (sP-selectin), a marker of platelet activation. We compared flow cytometry platelet activation in MetS+ and MetS- using the Mann Whitney test and the median test to compare sP-selectin and cognitive measures. We also measured the correlation between platelet activation and cognition using Spearman's rho correlation. Results: Platelet activation was significantly higher in MetS+ than MetS- (mean rank 8.60 vs. 3.83, p=0.017). Median score for the picture vocabulary test (language ability) was significantly lower in MetS+ relative to MetS- (82.35 vs. 104, p=0.015). In addition, platelet activation correlated negatively (rho = -0.74, p= 0.009) with the Wechsler Memory Scale: Spatial Span (nonverbal working memory) and plasma sP-selectin correlated negatively (rho = -0.55, p= 0.029) with the List Sorting Working Memory Test. Conclusion: Our preliminary findings suggest that platelet activation is involved in the association of MetS with cognitive impairment in patients with schizophrenia. Future studies are needed to elucidate the role of platelets in MetS-related cognitive impairment in patients with schizophrenia.

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“…They also observed that the SELP-PSGL-1 axis drove microglia towards a more immunosuppressive phenotype with increased expression of ARG-1, IL-10 and TGB-β in animal studies [ 130 ]. Despite these promising preclinical results, and although P-selectin monoclonal antibody is accepted by FDA for use in sickle cell anemia to prevent pain crisis [ 190 ], clinical trials are not yet being initiated for glioma treatment.…”

Section: Therapeutic Options For Targeting Tamsmentioning

confidence: 99%

Tumor-Associated Macrophages in Gliomas—Basic Insights and Treatment Opportunities

Andersen

Miletić

Hossain

2022

Cancers

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Glioma refers to a group of primary brain tumors which includes glioblastoma (GBM), astrocytoma and oligodendroglioma as major entities. Among these, GBM is the most frequent and most malignant one. The highly infiltrative nature of gliomas, and their intrinsic intra- and intertumoral heterogeneity, pose challenges towards developing effective treatments. The glioma microenvironment, in addition, is also thought to play a critical role during tumor development and treatment course. Unlike most other solid tumors, the glioma microenvironment is dominated by macrophages and microglia—collectively known as tumor-associated macrophages (TAMs). TAMs, like their homeostatic counterparts, are plastic in nature and can polarize to either pro-inflammatory or immunosuppressive states. Many lines of evidence suggest that immunosuppressive TAMs dominate the glioma microenvironment, which fosters tumor development, contributes to tumor aggressiveness and recurrence and, very importantly, impedes the therapeutic effect of various treatment regimens. However, through the development of new therapeutic strategies, TAMs can potentially be shifted towards a proinflammatory state which is of great therapeutic interest. In this review, we will discuss various aspects of TAMs in the context of glioma. The focus will be on the basic biology of TAMs in the central nervous system (CNS), potential biomarkers, critical evaluation of model systems for studying TAMs and finally, special attention will be given to the potential targeted therapeutic options that involve the TAM compartment in gliomas.

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P-Selectin Blockade in the Treatment of Painful Vaso-Occlusive Crises in Sickle Cell Disease: A Spotlight on Crizanlizumab

Cited by 20 publications

References 54 publications

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

The Role of P-Selectin in COVID-19 Coagulopathy: An Updated Review

Is platelet activation a link between metabolic syndrome and cognitive impairment in patients with schizophrenia?

Tumor-Associated Macrophages in Gliomas—Basic Insights and Treatment Opportunities

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