Platelet Signaling

Stalker, Timothy J.; Newman, Debra K.; Ma, Peisong; Wannemacher, Kenneth M.; Brass, Lawrence F.

doi:10.1007/978-3-642-29423-5_3

Cited by 139 publications

(164 citation statements)

References 93 publications

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“…PAR4 -это низкоаффинный рецептор, связывание тромбина с PAR4 вносит вклад в активацию тромбоцитов, главным образом, в условиях ингибирования или десенситизации PAR1. Предполагается, что главная функция PAR4 состоит в обеспечении избыточного состояния активации тромбоцитов тромбином, как одного из наиболее важных путей тромбоцитарного гемостаза [42][43][44][45][46][47]. Также известно, что PAR1 и PAR4 обладают разной кинетикой активации тромбоцитов.…”

Section: активация тромбоцитов тромбиномunclassified

“…Активированная Rho-киназа стимулирует фосфорилирование легких цепей миозина MLC (Myosin Light Chain) [56,57] и таким образом участвет в изменении формы цитоскелета. Кроме того, RhoA напрямую участвует в секреции гранул [42,52].…”

Section: активация тромбоцитов тромбиномunclassified

“…Образованные в результате действия PLCb DAG и IP3 также принимают участие в сигнализации "изнутри-наружу" при участии интегринов [42,51,[66][67][68].…”

Section: активация тромбоцитов при воздействии Adpunclassified

“…У P2Y 1 -/-мышей наблюдается незначительное увеличение продолжительности времени кровотечения, и возрастает устойчивость к тромбоэмболии, вызываемой введением ADP. Но у них не наблюдается предрасположенности к спонтанным кровотечениям [42].…”

Section: активация тромбоцитов при воздействии Adpunclassified

“…Они сохраняют способность изменять свою форму и активацию PLC, но это связано с нормальной работой P2Y 1 рецептора. У таких тромбоцитов наблюдается снижение способности к ингибированию формирования cAMP в ответ на ADP [42].…”

Section: активация тромбоцитов при воздействии Adpunclassified

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Activators, receptors and signal transduction pathways of blood platelets

et al. 2014

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Platelet participation in hemostatic plug formation requires transition into an activated state (or, rather, variety of states) upon action of agonists like ADP, thromboxane A , collagen, thrombin, and others. The mechanisms of action for different agonists, their receptors and signaling pathways associated with them, as well as the mechanisms of platelet response inhibition are the subject of the present review. Collagen exposed upon vessel wall damage induced initial platelet attachment and start of thrombus formation, which involves numerous processes such as aggregation, activation of integrins, granule secretion and increase of intracellular Ca2+. Thrombin, ADP, thromboxane A , and ATP activated platelets that were not initially in contact with the wall and induce additional secretion of activating substances. Vascular endothelium and secretory organs also affect platelet activation, producing both positive (adrenaline) and negative (prostacyclin, nitric oxide) regulators, thereby determining the relation of activation and inhibition signals, which plays a significant role in the formation of platelet aggregate under normal and pathological conditions. The pathways of platelet signaling are still incompletely understood, and their exploration presents an important objective both for basic cell biology and for the development of new drugs, the methods of diagnostics and of treatment of hemostasis disorders.

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Section: активация тромбоцитов тромбиномunclassified

Section: активация тромбоцитов при воздействии Adpunclassified

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Activators, receptors and signal transduction pathways of blood platelets

et al. 2014

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Human Blood Platelets and Their Role in the Development of Cardiovascular Disease

2018

Nutraceuticals and Human Blood Platelet Function

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Differences in the Platelet mRNA Landscape Portend Racial Disparities in Platelet Function and Suggest Novel Therapeutic Targets

Garofano

Park

Alarcón

et al. 2021

Clin Pharma and Therapeutics

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The African American (AA) population displays a 1.6 to 3‐fold higher incidence of thrombosis and stroke mortality compared with European Americans (EAs). Current antiplatelet therapies target the ADP‐mediated signaling pathway, which displays significant pharmacogenetic variation for platelet reactivity. The focus of this study was to define underlying population differences in platelet function in an effort to identify novel molecular targets for future antiplatelet therapy. We performed deep coverage RNA‐Seq to compare gene expression levels in platelets derived from a cohort of healthy volunteers defined by ancestry determination. We identified > 13,000 expressed platelet genes of which 480 were significantly differentially expressed genes (DEGs) between AAs and EAs. DEGs encoding proteins known or predicted to modulate platelet aggregation, morphology, or platelet count were upregulated in AA platelets. Numerous G‐protein coupled receptors, ion channels, and pro‐inflammatory cytokines not previously associated with platelet function were likewise differentially expressed. Many of the signaling proteins represent potential pharmacologic targets of intervention. Notably, we confirmed the differential expression of cytokines IL32 and PROK2 in an independent cohort by quantitative real‐time polymerase chain reaction, and provide functional validation of the opposing actions of these two cytokines on collagen‐induced AA platelet aggregation. Using Genotype‐Tissue Expression whole blood data, we identified 516 expression quantitative trait locuses with Fst values > 0.25, suggesting that population‐differentiated alleles may contribute to differences in gene expression. This study identifies gene expression differences at the population level that may affect platelet function and serve as potential biomarkers to identify cardiovascular disease risk. Additionally, our analysis uncovers candidate novel druggable targets for future antiplatelet therapies.

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Platelet Signaling

Cited by 139 publications

References 93 publications

Activators, receptors and signal transduction pathways of blood platelets

Activators, receptors and signal transduction pathways of blood platelets

Human Blood Platelets and Their Role in the Development of Cardiovascular Disease

Differences in the Platelet mRNA Landscape Portend Racial Disparities in Platelet Function and Suggest Novel Therapeutic Targets

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