Increasing susceptibility of nitric oxide–mediated inhibitory platelet signaling during storage of apheresis‐derived platelet concentrates

Kobsar, Anna; Klinker, Erdwine; Kühn, Sabine; Koessler, Angela; Yılmaz, Pınar Diydem; Boeck, Markus; Koessler, Juergen

doi:10.1111/trf.12584

Cited by 9 publications

(8 citation statements)

References 23 publications

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“…NO has been found to have a role in the regulation of the vascular system. For instance, it may inhibit platelet aggregation, leukocyte chemotaxis, as well as endothelial cell apoptosis (20,21). In addition, NO has been revealed to suppress VSMC proliferation in vitro (22).…”

Section: Discussionmentioning

confidence: 99%

Ligustrazine attenuates the platelet-derived growth factor-BB-induced proliferation and migration of vascular smooth muscle cells by interrupting extracellular signal-regulated kinase and P38 mitogen-activated protein kinase pathways

Huang

et al. 2012

Molecular Medicine Reports

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The abnormal proliferation and migration of vascular smooth muscle cells (VSMCs) leads to intimal thickening of the aorta and is, therefore, important in the development of arteriosclerosis. As a result, the use of antiproliferative and antimigratory agents for VSMCs offers promise for the treatment of vascular disorders. Although several studies have demonstrated that ligustrazine may be used to treat heart and blood vessel diseases, the detailed mechanism underlying its actions remain to be elucidated. In the present study, the inhibitory effect of ligustrazine on platelet-derived growth factor (PDGF)-BB-stimulated VSMC proliferation and migration, and the underlying mechanisms were investigated. The findings demonstrated that ligustrazine significantly inhibited PDGF-BB-stimulated VSMC proliferation. VSMCs dedifferentiated into a proliferative phenotype under PDGF-BB stimulation, which was effectively reversed by the administration of ligustrazine. In addition, ligustrazine also downregulated the production of nitric oxide and cyclic guanine monophosphate, induced by PDGF-BB. Additionally, ligustrazine significantly inhibited PDGF-BB-stimulated VSMC migration. Mechanistic investigation indicated that the upregulation of cell cycle-associated proteins and the activation of the extracellular signal-regulated kinase (ERK) and P38 mitogen-activated protein kinase (MAPK) signaling induced by PDGF-BB was suppressed by the administration of ligustrazine. In conclusion, the present study, demonstrated for the first time, to the best of our knowledge, that ligustrazine downregulated PDGF-BB-induced VSMC proliferation and migration partly, at least, through inhibiting the activation of the ERK and P38 MAPK signaling.

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Section: Discussionmentioning

confidence: 99%

Ligustrazine attenuates the platelet-derived growth factor-BB-induced proliferation and migration of vascular smooth muscle cells by interrupting extracellular signal-regulated kinase and P38 mitogen-activated protein kinase pathways

Huang

et al. 2012

Molecular Medicine Reports

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“…Early studies found that storage-induced decreases in thrombin sensitivity were linked to reduced high affinity thrombin binding sites [32]. [35]. Furthermore, basal cGMP concentration and VASP-phosphorylation rises by four to five times and 1.5 times respectively over 5 days of in vitro storage [36].…”

Section: Platelet Surface Receptor Modificationsmentioning

confidence: 99%

Platelet Storage Lesions: What More Do We Know Now?

Tung

Fraser

2018

Transfusion Medicine Reviews

108

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Platelet concentrate (PC) transfusions are a lifesaving adjunct to control and prevent bleeding in cancer, hematologic, surgical, and trauma patients. Platelet concentrate availability and safety are limited by the development of platelet storage lesions (PSLs) and risk of bacterial contamination. Platelet storage lesions are a series of biochemical, structural, and functional changes that occur from blood collection to transfusion. Understanding of PSLs is key for devising interventions that prolong PC shelf life to improve PC access and wastage. This article will review advancements in clinical and mechanistic PSL research. In brief, exposure to artificial surfaces and high centrifugation forces during PC preparation initiate PSLs by causing platelet activation, fragmentation, and biochemical release. During room temperature storage, enhanced glycolysis and reduced mitochondrial function lead to glucose depletion, lactate accumulation, and product acidification. Impaired adenosine triphosphate generation reduces platelet capacity to perform energetically demanding processes such as hypotonic stress responses and activation/aggregation. Storage-induced alterations in platelet surface proteins such as thrombin receptors and glycoproteins decrease platelet aggregation. During storage, there is an accumulation of immunoactive proteins such as leukocyte-derive cytokines (tumor necrosis factor α, interleukin (IL) 1α, IL-6, IL-8) and soluble CD40 ligand which can participate in transfusion-related acute lung injury and nonhemolytic transfusion reactions. Storage-induced microparticles have been linked to enhanced platelet aggregation and immune system modulation. Clinically, stored PCs have been correlated with reduced corrected count increment, posttransfusion platelet recovery, and survival across multiple meta-analyses. Fresh PC transfusions have been associated with superior platelet function in vivo; however, these differences were abrogated after a period of circulation. There is currently insufficient evidence to discern the effect of PSLs on transfusion safety. Various bag and storage media changes have been proposed to reduce glycolysis and platelet activation during room temperature storage. Moreover, cryopreservation and cold storage have been proposed as potential methods to prolong PC shelf life by reducing platelet metabolism and bacterial proliferation. However, further work is required to elucidate and manage the PSLs specific to these storage protocols before its implementation in blood banks.

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“…16 In addition, the surface proteins expressed on stored PLTs change over time, affecting their thrombin sensitivity, and they become more sensitized to nitric oxide, which impairs their ability to aggregate. [17][18][19] Counter to the reduced aggregation with increased storage time, the accumulation of PLT microparticles amplifies thrombin formation. 20 All of these changes may impact the clinical outcomes of patients receiving PLT transfusions of differing storage age.…”

Section: Discussionmentioning

confidence: 99%

Effect of platelet storage duration on clinical outcomes and incremental platelet change in critically ill children

et al. 2020

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Background The safety of platelet (PLT) concentrates with longer storage duration has been questioned due to biochemical and functional changes that occur during blood collection and storage. Some studies have suggested that transfusion efficacy is decreased and immune system dysfunction is worsened with increased storage age. We sought to describe the effect of PLT storage age on laboratory and clinical outcomes in critically ill children receiving PLT transfusions. Study Design and Methods: We performed a secondary analysis of a prospective, observational point-prevalence study. Children (3 days to 16 years of age) from 82 pediatric intensive care units in 16 countries were enrolled if they received a PLT transfusion during one of the predefined screening weeks. Outcomes (including PLT count increments, organ dysfunction, and transfusion reactions) were evaluated by PLT storage age. Results: Data from 497 patients were analyzed. The age of the PLT transfusions ranged from 1 to 7 days but the majority were 4 (24%) or 5 (36%) days of age. Nearly two-thirds of PLT concentrates were transfused to prevent bleeding. The indication for transfusion did not differ between storage age groups Abbreviations: IQR, interquartile range; PICU, pediatric intensive care unit. †The P 3 T investigators are listed in the acknowledgements.

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Increasing susceptibility of nitric oxide–mediated inhibitory platelet signaling during storage of apheresis‐derived platelet concentrates

Cited by 9 publications

References 23 publications

Ligustrazine attenuates the platelet-derived growth factor-BB-induced proliferation and migration of vascular smooth muscle cells by interrupting extracellular signal-regulated kinase and P38 mitogen-activated protein kinase pathways

Ligustrazine attenuates the platelet-derived growth factor-BB-induced proliferation and migration of vascular smooth muscle cells by interrupting extracellular signal-regulated kinase and P38 mitogen-activated protein kinase pathways

Platelet Storage Lesions: What More Do We Know Now?

Effect of platelet storage duration on clinical outcomes and incremental platelet change in critically ill children

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