Platelet Activation and Endothelial Cell Dysfunction

Poll, Tom van der; Parker, Robert I.

doi:10.1016/j.ccc.2019.11.002

Cited by 36 publications

(60 citation statements)

References 80 publications

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“…Many interaction pathways convey on the endothelial cell surface linking these two cellular components in the initiation and regulation of hemostasis and inflammation. Inflammation causes the stimulation of both platelets and endothelial cells, affecting not only their role in hemostasis, but also in the immune response [180]. The feedback between endothelial and platelet dysfunctions play a definite role in the alteration of the immune system in patients with uremia.…”

Section: Uremia Platelet Dysfunction and Alterations In Immunitymentioning

confidence: 99%

Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease

Díaz‐Ricart

Torramadé-Moix

Pascual

et al. 2020

Toxins

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Chronic kidney disease (CKD) patients have an accelerated atherosclerosis, increased risk of thrombotic-ischemic complications, and excessive mortality rates when compared with the general population. There is also evidence of an endothelial damage in which the proinflammatory state, the enhanced oxidative stress, or the accumulation of toxins due to their reduced renal clearance in uremia play a role. Further, there is evidence that uremic endothelial cells are both involved in and victims of the activation of the innate immunity. Uremic endothelial cells produce danger associated molecular patterns (DAMPS), which by binding to specific pattern recognition receptors expressed in multiple cells, including endothelial cells, induce the expression of adhesion molecules, the production of proinflammatory cytokines and an enhanced production of reactive oxygen species in endothelial cells, which constitute a link between immunity and inflammation. The connection between endothelial damage, inflammation and defective immunity in uremia will be reviewed here.

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Section: Uremia Platelet Dysfunction and Alterations In Immunitymentioning

confidence: 99%

Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease

Díaz‐Ricart

Torramadé-Moix

Pascual

et al. 2020

Toxins

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“…Despite the roles of platelets in hemostasis and thrombosis, their roles in regulating inflammation and immunity have gained increasing attentions in recent years (Maurer et al, 2020;Rayes et al, 2020;van der Poll and Parker, 2020). Platelets have been recognized as crucial regulators of inflammatory processes under various pathophysiological conditions (Karhausen et al, 2020).…”

Section: Introductionmentioning

confidence: 99%

Associations of Platelet Count with Inflammation and Response to Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis

et al. 2020

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Background: Increased platelet count has been reported in ankylosing spondylitis (AS) patients, but its clinical significance is still largely elusive. The objective of this study was to evaluate the clinical role of platelet count in AS patients, especially its impact on treatment outcomes. Methods: A case-control study containing 35 AS patients receiving anti-tumor necrosis factor-α (anti-TNF-α) therapy and 45 healthy controls was performed, and AS patients were followed at least 6 months after anti-TNF-α therapy. A systematic review and metaanalysis of studies containing relevant data on outcomes of interest was also performed. Results: AS patients had significantly higher platelet count than controls (p 0.0001), and the significantly increased platelet count in AS patients was confirmed in a metaanalysis of 14 studies involving 1,223 AS patients and 913 controls (mean difference 39.61, 95% CI 27.89-51.34, p < 0.001). Besides, platelet count was significantly correlated with ESR (p < 0.001) and was moderately correlated with ASDAS-CRP score (p 0.002). Moreover, anti-TNF-α therapy could reduce platelet count in AS patients at the first month and the effect was maintained through the treatment duration. In the prospective follow-up study of those 35 AS patients, those responders to anti-TNF-α therapy had significantly lower platelet count than nonresponders (p 0.015). Logistic regression analysis suggested that lower platelet count was associated with higher possibility of achieving good response to anti-TNF-α therapy in AS patients (odds ratio 2.26; 95% CI 1.06-4.82; p 0.035). Conclusion: This study suggested that platelet count was associated with inflammation severity and treatment outcomes in AS patients, and elevated platelet count was a promising biomarker of poorer response to anti-TNF-α therapy. The findings above need to be validated in more future studies.

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“…After stimulation with thrombin, some PLPs become irregularly shaped with membrane protrusions and filopods. Besides the similarities in morphological changes, PLPs are also similar to human platelets in terms of thrombin-induced aggregation function and CD62P and GPIIb/IIIa expression (Takeuchi et al, 1998).…”

Section: Discussionmentioning

confidence: 89%

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity

et al. 2020

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Platelets are derived from megakaryocytes and play an important role in blood coagulation. By using high throughput sequencing, we have found that the long non-coding RNA (lncRNA) nuclear paraspeckle assembly transcript 1 (NEAT1) is abundant in platelets (GEO ID: 200097348). However, little is known about its role in regulating megakaryocyte differentiation and platelet activity. This study aims to clarify the effect of NEAT1 on MEG-01 differentiation and platelet-like particle (PLP) activity. NEAT1 in MEG-01 cells was knocked down by siRNA transfection. The adhesion of MEG-01 and PLP to collagen-coated coverslips was observed under a fluorescence microscope. Flow cytometry was used to investigate cell apoptosis, cell cycle, the levels of D41/CD42b on MEG-01 cells and CD62P on PLPs. Quantitative real-time polymerase chain reaction was used to detect NEAT1 and IL-8 expression levels. Western blot was used to measure the protein levels of Bcl-2, Bax, cleaved caspase-3, and IL-8. RNA-binding protein immunoprecipitation was used to detect the interaction of NEAT1 and splicing factor proline/glutamine-rich (SFPQ). Results showed that NEAT1 knockdown decreased the adhesion ability of thrombinstimulated MEG-01 and PLP. The expression of CD62P on PLPs and CD41/CD42b on MEG-01 cells was inhibited by NEAT1 knockdown. In addition, NEAT1 knockdown inhibited cell apoptosis with increased Bcl2/Bax ratio and decreased cleaved caspase-3, and reduced the percentage of cells in the G0/G1 phase. Meanwhile, NEAT1 knockdown inhibited the expression of IL-8. A strong interaction of NEAT1 and SFPQ, a transcriptional repressor of IL-8, was identified. NEAT1 knockdown reduced the interaction between SFPQ and NEAT1.The results suggest that lncRNA NEAT1 knockdown decreases MEG-01 differentiation, PLP activity, and IL-8 level. The results also indicate that the regulation of NEAT1 on IL-8 may be realized via a direct interaction between NEAT1 and SFPQ.

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Platelet Activation and Endothelial Cell Dysfunction

Cited by 36 publications

References 80 publications

Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease

Endothelial Damage, Inflammation and Immunity in Chronic Kidney Disease

Associations of Platelet Count with Inflammation and Response to Anti-TNF-α Therapy in Patients with Ankylosing Spondylitis

Downregulation of Long Non-coding RNA Nuclear Paraspeckle Assembly Transcript 1 Inhibits MEG-01 Differentiation and Platelet-Like Particles Activity

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