Platelet PAR1 receptor density—Correlation to platelet activation response and changes in exposure after platelet activation

Ramström, Sofia; Öberg, Karin Vretenbrant; Åkerström, Finn; Enström, Camilla; Lindahl, Tomas

doi:10.1016/j.thromres.2007.06.010

Cited by 31 publications

(25 citation statements)

References 19 publications

(12 reference statements)

Supporting

Mentioning

Contrasting

Order By: Relevance

“…The PAR 1 receptor number variability and its relation to the degree of platelet activation is known [48], though its specific effects on the platelet subpopulation formation were not studied. Variation of other key parameters (such as number of different signaling molecules) or even simply stochastic nature of calcium signaling can also induce divergence of platelets into subpopulations as was investigated in our previous work [20] that suggested that main phenomena of PS + platelet formation do not depend on the nature of this specific factor as they are determined by the strong nonlinearity of mitochondrial collapse response.…”

Section: Discussionmentioning

confidence: 99%

“…Although platelet subpopulations can be modeled by variation of different platelet proteins, for this purpose we used the assumption that PAR 1 receptors are distributed normally in platelet population and its mean value equals 2000 per cell [47,48]. We determined a minimal value Δ ψ* of mitochondrial potential Δ ψ for the necessary percentage of PS + platelets, by fitting to experimental data point (for example, platelets activation by 200 μM of SFLLRN causes formation of 2.5% PS + platelets) and by using PAR 1 receptors normal distribution (Fig.…”

Section: Model Overviewmentioning

confidence: 99%

See 1 more Smart Citation

Modulation and pre-amplification of PAR1 signaling by ADP acting via the P2Y12 receptor during platelet subpopulation formation

Шахиджанов

Shaturny

Panteleev

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

Section: Discussionmentioning

confidence: 99%

Section: Model Overviewmentioning

confidence: 99%

Modulation and pre-amplification of PAR1 signaling by ADP acting via the P2Y12 receptor during platelet subpopulation formation

Шахиджанов

Shaturny

Panteleev

et al. 2015

Biochimica et Biophysica Acta (BBA) - General Subjects

View full text Add to dashboard Cite

“…Then, activated platelets cause the Weibel-Palade body release leading to CD62-P mediated leukocyte rolling, suggesting that platelet CD62-P promotes development of inflammation and deterioration of AS [25–27]. On the other hand, fibrinogen deposition stimulates chemokine secretion and facilitates a neutrophil-endothelial interaction in septic shock [16, 28].…”

Section: Discussionmentioning

confidence: 99%

All-trans-Retinoic Acid Ameliorated High Fat Diet-Induced Atherosclerosis in Rabbits by Inhibiting Platelet Activation and Inflammation

Zhou

Pan

et al. 2012

Journal of Biomedicine and Biotechnology

View full text Add to dashboard Cite

Background. All-trans-retinoic acid (atRA) is effective for many proliferative diseases. We investigated the protective effects of atRA against atherosclerosis. Methods. Rabbits were randomly allocated to receive basal diet or an HFD for 4 weeks. HFD group then received rosuvastatin (3 mg/day), atRA (5 mg/kg/day), or the same volume of vehicle, respectively, for next 8 weeks. Results. HFD group showed increases in plasma lipids and aortic plaque formation. P-selectin expression and fibrinogen binding on platelets or deposition on the intima of the aorta also increased significantly as did the levels of TNF-α, IL-6, and fibrinogen in plasma. After 8 weeks of treatment with atRA, there was a significant decrease in plasma lipids and improvement in aortic lesions. AtRA also inhibited the expression of P-selectin and fibrinogen binding on platelets and deposition on the intima of the aorta. Conclusion. AtRA can ameliorate HFD-induced AS in rabbits by inhibiting platelet activation and inflammation.

show abstract

“…Measurements were performed as described previously in detail [17] using a Coulter Epics XL.MCL flow cytometer and Expo 32 ADC software (Beckman Coulter). For the experimental procedure, the Platelet Calibrator kit from Biocytex and the monoclonal anti-PAR1 antibody WEDE15 (Immunotech) were used.…”

Section: Par1 Surface Expressionmentioning

confidence: 99%

Protease-activated receptor 1 (PAR1) signalling desensitization is counteracted via PAR4 signalling in human platelets

Fälker

Haglund

Gunnarsson

et al. 2011

Biochemical Journal

View full text Add to dashboard Cite

PARs (protease-activated receptors) 1 and 4 belong to the family of G-protein-coupled receptors which induce both G(α12/13) and G(αq) signalling. By applying the specific PAR1- and PAR4-activating hexapeptides, SFLLRN and AYPGKF respectively, we found that aggregation of isolated human platelets mediated via PAR1, but not via PAR4, is abolished upon homologous receptor activation in a concentration- and time-dependent fashion. This effect was not due to receptor internalization, but to a decrease in Ca²⁺ mobilization, PKC (protein kinase C) signalling and α-granule secretion, as well as to a complete lack of dense granule secretion. Interestingly, subthreshold PAR4 activation rapidly abrogated PAR1 signalling desensitization by differentially reconstituting these affected signalling events and functional responses, which was sufficient to re-establish aggregation. The lack of ADP release and P2Y₁₂ receptor-induced G(αi) signalling accounted for the loss of the aggregation response, as mimicking G(αi/z) signalling with 2-MeS-ADP (2-methylthioadenosine-5'-O-diphosphate) or epinephrine (adrenaline) could substitute for intermediate PAR4 activation. Finally, we found that the re-sensitization of PAR1 signalling-induced aggregation via PAR4 relied on PKC-mediated release of both ADP from dense granules and fibrinogen from α-granules. The present study elucidates further differences in human platelet PAR signalling regulation and provides evidence for a cross-talk in which PAR4 signalling counteracts mechanisms involved in PAR1 signalling down-regulation.

show abstract

Platelet PAR1 receptor density—Correlation to platelet activation response and changes in exposure after platelet activation

Cited by 31 publications

References 19 publications

Modulation and pre-amplification of PAR1 signaling by ADP acting via the P2Y12 receptor during platelet subpopulation formation

Modulation and pre-amplification of PAR1 signaling by ADP acting via the P2Y12 receptor during platelet subpopulation formation

All-trans-Retinoic Acid Ameliorated High Fat Diet-Induced Atherosclerosis in Rabbits by Inhibiting Platelet Activation and Inflammation

Protease-activated receptor 1 (PAR1) signalling desensitization is counteracted via PAR4 signalling in human platelets

Contact Info

Product

Resources

About