Platelet Hyperreactivity in Diabetes: Focus on GPVI Signaling—Are Useful Drugs Already Available?

Arthur, Jane Frances; Jandeleit-Dahm, Karin; Andrews, Robert K.

doi:10.2337/db16-1098

Cited by 27 publications

(23 citation statements)

References 52 publications

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“…Recent research has focused on the plateletspecific collagen receptor, glycoprotein VI (GPVI), as a potential antiplatelet target. Signaling events downstream from GPVI are influenced by hyperglycemia, oxidative stress, and shear stress [19]. According to previous investigations, SAA has extensive pharmacological effects, including antidiabetic [11], antioxidant [8] and other effects.…”

Section: Discussionmentioning

confidence: 99%

“…Platelets obtained from DM2 are hyperactive and demonstrate exaggerated aggregation as well as thrombus generation [15]. There are many different mechanisms that have been attributed to the diabetes-associated enhanced platelet activation [16], such as a loss of the antiplatelet effect of insulin [17], high blood glucose, oxidative stress [18], elevated vascular shear forces [19], increased binding of fibrinogen [20], altered expression of glycoprotein receptors and proteins attached to the platelet surface [21][22][23]. It is clear, from the literature, that there is an increased expression of platelet activation makers, such as CD62p and PAC-1, as measured by flow cytometry in DM2, which contributes to the progression of thrombotic and CVD events.…”

Section: Discussionmentioning

confidence: 99%

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Salvianolic acid a inhibits platelet activation and aggregation in patients with type 2 diabetes mellitus

Zhou

Xiang

Liu

et al. 2020

BMC Cardiovasc Disord

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Background: Platelets in patients with type 2 diabetes mellitus (DM2) are characterized by increased activation and aggregation, which tends to be associated with a high morbidity and mortality due to cardiovascular disease (CVD). Moreover, a large proportion of DM2 patients show an inadequate response to standard antiplatelet treatments, contributing to recurrent cardiovascular events. In our previous study, we indicated that Salvianolic acid A (SAA) presents an antiplatelet effect in healthy volunteers. However, whether it can inhibit "activated platelets" with a pathologic status has not been explored. Therefore, this study was designed to investigate the antiplatelet effect of SAA and its diabetic complication-related difference in DM2.Methods: Forty patients diagnosed with DM2 from January 2018 to April 2018 were recruited. Fibrinogen-binding (PAC-1) and P-selectin (CD62p) flow cytometry reagents were measured under resting and stimulated conditions by flow cytometry, while agonist-induced platelet aggregation was conducted by light transmission aggregometry. Before all these measurements were conducted, all platelet samples were preincubated with a vehicle or SAA for 10 min. Additionally, the diabetic complication-related difference in the antiplatelet effect of SAA was further studied in enrolled patients. Results:The expressions of PAC-1 and CD62p were elevated in DM2, as well as the maximal platelet aggregation. In addition, SAA decreased the expressions of PAC-1 and CD62p, which were enhanced by ADP and thrombin (all P < 0.01). It also reduced the platelet aggregation induced by ADP (P < 0.001) and thrombin (P < 0.05). Comparing the antiplatelet effect of SAA on DM2, with and without diabetic complications, no statistically significant difference was found (all P > 0.05). Conclusions:The present study demonstrated that SAA can inhibit platelet activation and aggregation in patients with DM2, and the inhibition did not abate for the existence of diabetic complications.

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Section: Discussionmentioning

confidence: 99%

Section: Discussionmentioning

confidence: 99%

Salvianolic acid a inhibits platelet activation and aggregation in patients with type 2 diabetes mellitus

Zhou

Xiang

Liu

et al. 2020

BMC Cardiovasc Disord

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“…Finally, platelet hyper‐reactivity in diabetes ‐ where VLUs are more prevalent and the use of autologous PRP more indicated ‐ is associated with an increased platelet intracellular oxidative state coinciding with elevated levels of reactive oxygen species (ROS) known to be generated downstream of GPIbα/GPVI engagement . Whether such measurable parameters contribute mechanistically or predict poor wound healing in diabetic individuals, as well as the efficacy of autologous PRP in VLUs, has yet to be determined.…”

Section: Future Directionsmentioning

confidence: 99%

“…Finally, platelet hyper-reactivity in diabetes -where VLUs are more prevalent and the use of autologous PRP more indicated -is associated with an increased platelet intracellular oxidative state coinciding with elevated levels of reactive oxygen species (ROS) known to be generated downstream of GPIbα/GPVI engagement. [51][52][53][54] Whether such measurable parameters contribute mechanistically or predict poor wound healing in diabetic individuals, as well as the efficacy of autologous PRP in VLUs, has yet to be determined. In addition, although not considered in detail here, non-autologous allogeneic healthy donor PRP or serum, with associated quality control and product development to define levels of growth factors within optimal ranges, could also be relevant to the use of PRP in ulcers and provide a future alternative therapy to using autologous PRP.…”

Section: Future Directionsmentioning

confidence: 99%

Autologous platelet‐rich plasma for healing chronic venous leg ulcers: Clinical efficacy and potential mechanisms

Weller

Gardiner

Arthur

et al. 2019

International Wound Journal

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The overall quality of evidence of autologous platelet‐rich plasma (PRP) for treating chronic wounds remains low. While further well‐designed clinical studies are clearly required to convincingly demonstrate the efficacy of autologous PRP in improved healing of venous leg ulcers (VLUs) and other chronic wounds, there is also an increasing need to better define the underlying mechanisms of action and whether positive outcomes can be predicted based on the analysis of PRP. This brief review will discuss the current understanding of autologous PRP in VLUs and whether molecular evaluation of PRP at the time of collection could potentially be informative to clinical outcomes. Benefits of the autologous PRP treatment strategy include that PRP is easily accessible and is relatively inexpensive and safe. Better understanding of the mechanisms involved could improve treatment, enable supplementation, and/or lead to gains in product development. Analysis of PRP could also add value to future clinical trials on efficacy and potentially personalised treatment regimens.

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“…Reactive oxygen species production caused by downstream of GPVI signaling is proportionally exaggerated in elevated glucose levels. 117 Chronic hyperglycemia affects calcium homeostasis by enhancing the calcium influx as a response to collagen and thrombin, thus fostering platelet adhesion. 118 Insulin normally exerts an antiaggregating effect on platelets, by means of inhibiting calcium mobilization.…”

Section: Gestational Diabetes Mellitusmentioning

confidence: 99%

High-Risk Pregnancies and Their Impact on Neonatal Primary Hemostasis

Politou

Mougiou

Kollia

et al. 2019

Semin Thromb Hemost

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Primary hemostasis, similar to other systems in the adjusting and transitioning neonate, undergoes developmental adaptations in the first days of life. Although platelets of neonates do not differ quantitatively compared with those of adults, they functionally present with major differences, thus supporting the theory of a “hypofunctional” phenotype that is counterbalanced by high hematocrit and more potent von Willebrand factor multimers. No clinical effect of bleeding tendency has hence been established so far for healthy term neonates. However, discrepancies in functionality have been noted, associated with gestational age, with more pronounced platelet hyporesponsiveness in preterm neonates. Multiple methods of in vitro platelet function evaluation such as PFA-100/200, platelet aggregometry, flow cytometry, and cone and platelet analyzer have been used for assessment of neonatal primary hemostasis. Several pregnancies are characterized as “high-risk” when risk factors preexist in maternal history or evolve during pregnancy. These pregnancies require specialized observation as they may have unpredictable outcome. High-risk pregnancies include clinical entities such as preeclampsia, pregnancy-induced smoking during pregnancy, gestational diabetes mellitus (GDM), autoimmune diseases, and other maternal hematological conditions. In some cases, like systemic lupus erythematosus, antiphospholipid antibody syndrome, and maternal immunologically based thrombocytopenia, neonatal thrombocytopenia is regarded as a prominent hemostasis defect, while in others, like pregnancy-induced hypertension and preeclampsia, both quantitative and qualitative disorders of neonatal platelets have been reported. In other pathologies, like GDM, neonatal primary hemostasis remains vastly unexplored, which raises the need for further investigation. The extent to which primary hemostasis is affected in neonates of high-risk pregnancies is the main objective of this narrative review.

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Platelet Hyperreactivity in Diabetes: Focus on GPVI Signaling—Are Useful Drugs Already Available?

Cited by 27 publications

References 52 publications

Salvianolic acid a inhibits platelet activation and aggregation in patients with type 2 diabetes mellitus

Salvianolic acid a inhibits platelet activation and aggregation in patients with type 2 diabetes mellitus

Autologous platelet‐rich plasma for healing chronic venous leg ulcers: Clinical efficacy and potential mechanisms

High-Risk Pregnancies and Their Impact on Neonatal Primary Hemostasis

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