A dichotomy in platelet activation: Evidence of different functional platelet responses to inflammatory versus haemostatic stimuli

Petito, Eleonora; Amison, Richard T.; Piselli, Elisa; Shah, Sajeel A.; Momi, Stefania; Pitchford, Simon; Gresele, Paolo; Page, Clive

doi:10.1016/j.thromres.2018.10.019

Cited by 21 publications

(22 citation statements)

References 48 publications

Supporting

Mentioning

Contrasting

Unclassified

Order By: Relevance

“…Activation of platelets or leucocytes led to PLA formation [ 50 ]. Biochemic substances associated with thrombosis, such as adenosine diphosphate (ADP), collagen, platelet-activating factor (PAF), and thrombin enhanced PLA level versus lack of stimulation [ 5 , 36 , 50 ]. Similarly, proinflammatory N-formyl-methionyl-leucyl-phenylalanine (fMLP), serotonin, and stromal cell-derived factor-1α (CXCL12) increased PLA formation versus lack of stimulation, but this effect was lower than induced by prothrombotic agents.…”

Section: Characteristics Of Platelet–leucocyte Aggregatesmentioning

confidence: 99%

“…PLA are defined as heterotypic combinations of at least one platelet with one leucocyte [ 4 ]. PLA are formed during immune or thrombotic reactions [ 5 ]. Hence, PLA have been investigated as potential biomarkers in many pathologies, including chronic obstructive pulmonary disease [ 6 ], antineutrophil cytoplasmic antibody (ANCA)-associated vasculitis [ 7 ], consumptive coagulopathy in xenotransplantation [ 8 ], cutaneous Arthus reactions [ 9 ], and infections [ 10 ]-among others COVID-19 [ 11 ]-and sepsis [ 12 ].…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

Platelet–Leucocyte Aggregates as Novel Biomarkers in Cardiovascular Diseases

Pluta

Porębska

Urbanowicz

et al. 2022

Biology

View full text Add to dashboard Cite

Platelet–leucocyte aggregates (PLA) are a formation of leucocytes and platelets bound by specific receptors. They arise in the condition of sheer stress, thrombosis, immune reaction, vessel injury, and the activation of leukocytes or platelets. PLA participate in cardiovascular diseases (CVD). Increased levels of PLA were revealed in acute and chronic coronary syndromes, carotid stenosis cardiovascular risk factors. Due to accessible, available, replicable, quick, and low-cost quantifying using flow cytometry, PLA constitute an ideal biomarker for clinical practice. PLA are promising in early diagnosing and estimating prognosis in patients with acute or chronic coronary syndromes treated by percutaneous coronary intervention (PCI) and coronary artery bypass grafting (CABG). PLA were also a reliable marker of platelet activity for monitoring antiplatelet therapy. PLA consist also targets potential therapies in CVD. All of the above potential clinical applications require further studies to validate methods of assay and proof clinical benefits.

show abstract

Section: Characteristics Of Platelet–leucocyte Aggregatesmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

Platelet–Leucocyte Aggregates as Novel Biomarkers in Cardiovascular Diseases

Pluta

Porębska

Urbanowicz

et al. 2022

Biology

View full text Add to dashboard Cite

show abstract

“…1 A) and PMN-platelet heteroaggregate formation (Fig. 1 B 38 ), which resulted in the increased amount of PMNs in thrombi. PMN attraction to the growing thrombi observed here has been previously demonstrated in vivo for another TLR4 agonist HMGB1 39 .…”

Section: Discussionmentioning

confidence: 97%

Effects of bacterial lipopolysaccharides on platelet function: inhibition of weak platelet activation

Martyanov

Maiorov

Filkova

et al. 2020

Sci Rep

View full text Add to dashboard Cite

Platelets are anucleate blood cells with reported roles in hemostasis and immune responses, which possess a functional receptor for bacterial lipopolysaccharides (LPSs), the well-known inducers of inflammation. However, LPSs effects on platelets are contradictory. Here we aim to investigate mechanisms of platelet functioning in the presence of LPS and to find the cause of the discrepancy in the previously published data. Cell activity was analyzed by flow cytometry, western blotting, and aggregometry. Thrombus growth was assessed by fluorescent microscopy. LPS' activity was checked by their capability to induce PMN activation. However, LPSs did not substantially affect either thrombus growth in flow chambers, irreversible platelet aggregation, or platelet responses to strong activation. Platelet aggregation in response to 1 μM of ADP was significantly inhibited by LPSs. Flow cytometry analysis revealed that platelet activation responses to weak stimulation were also diminished by LPSs, while VASP phosphorylation was weakly increased. Additionally, LPSs were capable of inhibition of ADP-induced P2-receptor desensitization. Incubation of platelets with a pan-PDE inhibitor IBMX significantly enhanced the LPSs-induced platelet inhibition, implying cAMP/cGMP dependent mechanism. The discrepancy in the previously published data could be explained by LPSinduced weak inhibition of platelet activation and the prevention of platelet desensitization. Lipopolysaccharides (LPSs) are the components of the outer membrane of the gram-negative bacteria 1 , which are recognized by the toll-like receptor 4 (TLR4) 2. LPS are among the most potent mediators of bacteria-induced sepsis and associated disseminated intravascular coagulation (DIC) 3. TLR4 was detected on the surface of myeloid cell line: granulocytes, monocytes, dendric cells 4. TLR4 is also expressed on the surface of platelets 5,6-anucleate blood cells, responsible for hemostasis 7. In order to recognize LPS, TLR4 requires such cofactor proteins as CD14, myeloid-differentiation factor 2 (MD2), and LPS binding protein (LBP) 8. Upon ligation and dimerization, TLR4 induces the formation of a "myddosome" signaling complex, which initiates nuclear factor kappa-B (NF-κB) intracellular signaling cascade 2,8,9. In anucleate platelets, the most important part of this cascade is the inhibitor of NF-κB (IκB), which has been reported to mediate granule secretion and other signalling events 8. LPS mediated TLR4 activation is claimed to enhance platelet stimulation by ADP and CRP 6,10,11. LPS also were shown to induce increased oxygen consumption by platelet mitochondria 5,12. LPS driven platelet activation is a potential mediator of neutrophil extracellular traps (NETosis) in vivo 8. Finally, it was reported that LPS are capable of inducing synthesis of IL1β in platelets 13. Platelet reactivity to LPS could be caused by activation of

show abstract

“…Platelets play a key role in the inflammatory response. [14][15][16] However, the role of P-selectin in systemic inflammation requires further investigation. We also evaluated other traditional risk factors and showed that BMI, TC, and TG were all increased and HDL-C was decreased in patients with CHD compared with controls.…”

Section: Discussionmentioning

confidence: 99%

“…Platelets play a key role in the inflammatory response. 14 – 16 However, the role of P-selectin in systemic inflammation requires further investigation.…”

Section: Discussionmentioning

confidence: 99%

Plasma P-selectin level is associated with severity of coronary heart disease in Chinese Han population

Song

Chang

et al. 2020

J Int Med Res

View full text Add to dashboard Cite

Objective This study aimed to evaluate the association between plasma P-selectin levels and the severity of coronary heart disease (CHD) in a Chinese Han population. Methods We enrolled 219 patients with CHD and 168 healthy individuals without CHD as a control group. Coronary stenosis was evaluated based on the number of diseased coronary arteries and the Gensini scoring system. P-selectin levels were quantified by enzyme-linked immunosorbent assay and the association between CHD and plasma P-selectin level was analyzed. Results P-selectin levels were significantly higher in CHD patients compared with controls. Levels were highest in patients with three-vessel disease and lowest in those with one-vessel disease, with significant differences among the groups. P-selectin levels were also highest in the high-score and lowest in the low-score group according to Gensini score, with significant differences among the groups. P-selectin level was significantly positively correlated with Gensini score and C-reactive protein level. Elevated P-selectin was identified as an independent risk factor for CHD. Conclusion P-selectin levels were increased in Chinese Han patients with CHD. P-selectin level is an independent risk factor for CHD and may serve as a biomarker reflecting the severity of CHD in the Chinese Han population.

show abstract

A dichotomy in platelet activation: Evidence of different functional platelet responses to inflammatory versus haemostatic stimuli

Cited by 21 publications

References 48 publications

Platelet–Leucocyte Aggregates as Novel Biomarkers in Cardiovascular Diseases

Platelet–Leucocyte Aggregates as Novel Biomarkers in Cardiovascular Diseases

Effects of bacterial lipopolysaccharides on platelet function: inhibition of weak platelet activation

Plasma P-selectin level is associated with severity of coronary heart disease in Chinese Han population

Contact Info

Product

Resources

About