Platelet secretion: From haemostasis to wound healing and beyond

Golebiewska, Ewelina M.; Poole, Alastair W.

doi:10.1016/j.blre.2014.10.003

Cited by 670 publications

(566 citation statements)

References 137 publications

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“…Despite the importance of dense-granule secretion in platelet function, 24 signaling pathways specifically regulating this process are not well defined. Although a definitive involvement of MAP3Ks remains to be elucidated, the present study showed that MINK1 acts upstream of MEK1/2, MKK3/6, p38, ERK, and Akt, sequentially and specifically regulating dense-granule secretion.…”

Section: Discussionmentioning

confidence: 99%

Misshapen/NIK-related kinase (MINK1) is involved in platelet function, hemostasis, and thrombus formation

Yue

Luo

et al. 2016

Blood

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Key Points• MINK1 promotes hemostasis and thrombosis in vivo.• MINK1 specifically regulates platelet dense-granule secretion.The sterile-20 kinase misshapen/Nck-interacting kinase (NIK)-related kinase 1 (MINK1) is involved in many important cellular processes such as growth, cytoskeletal rearrangement, and motility. Here, with MINK1-deficient (MINK1 2/2 ) mice, we showed that MINK1 plays an important role in hemostasis and thrombosis via the regulation of platelet functions. In the tail-bleeding assay, MINK12/2 mice exhibited a longer bleeding time than wild-type (WT) mice (575.2 6 59.7 seconds vs 419.6 6 66.9 seconds). In a model of ferric chloride-induced mesenteric arteriolar thrombosis, vessel occlusion times were twice as long in MINK1 2/2 mice as in WT mice. In an in vitro microfluidic whole-blood perfusion assay, thrombus formation on a collagen matrix under arterial shear conditions was significantly reduced in MINK1 2/2 platelets. Moreover, MINK1 2/2 platelets demonstrated impaired aggregation and secretion in response to low doses of thrombin and collagen. Furthermore, platelet spreading on fibrinogen was largely hampered in MINK1 2/2 platelets. The functional differences of MINK1 2/2 platelets could be attributed to impaired adenosine 59-diphosphate secretion. Signaling events associated with MINK1 appeared to involve extracellular signal-regulated kinase, p38, and Akt. Hence, MINK1 may be an important signaling molecule that mediates mitogen-activated protein kinase signaling and participates in platelet activation and thrombus formation. (Blood. 2016;127(7):927-937)

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Section: Discussionmentioning

confidence: 99%

Misshapen/NIK-related kinase (MINK1) is involved in platelet function, hemostasis, and thrombus formation

Yue

Luo

et al. 2016

Blood

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“…Gracias a modelos animales, ahora se sabe que la disminución de la actividad de la eNOS es parte fundamental de la fisiopatología de la hipertensión portal (18,19). Las plaquetas, además de servir como elemento celular en el tapón hemostático, poseen gránulos intracelulares con elementos capaces de modificar los procesos inflamatorios e inmunológicos dentro del hígado (10). Los gránulos α contienen factores de crecimiento cuya diana son las vías Akt (fosfatidilinositol-3-kinasa/AKT [PI3K-Akt]) y extracellular signal-regulated kinase (ERK) 1/2, ambas trascendentales para el hepatocito (20) al grado que recientes investigaciones sugieren que la transfusión de plaquetas puede mejorar la regeneración hepática (20,21).…”

Section: Alteraciones En La Hemostasia Primariaunclassified

Insuficiencia hepática crónica y hemostasia

Peñafiel

Sánchez

et al. 2017

Rev. Colomb. Gastroenterol.

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ResumenLa insuficiencia hepática es un estado patológico que condiciona la síntesis y metabolismo de diversas biomoléculas, siendo las alteraciones a la hemostasia una de las primeras consecuencias a nivel sistémico que se hacen presentes; debido a esto y por la dimensión de los riesgos de esta situación, no es raro que las pruebas de coagulación sean indispensables para formular las escalas pronósticas en pacientes hepatópatas.Los conocimientos sobre hemostasia han avanzado en la última década; la clásica cascada de activación de los factores de la coagulación ha sido perfeccionada hasta conformarse el ahora vigente modelo celular que considera la valiosa e indispensable participación del endotelio y las plaquetas. Gracias a esto es posible comprender que, en pacientes con insuficiencia hepática, el riesgo de sangrado no obedece únicamente a la deficiencia en la producción de los factores de la coagulación y, por tanto, es cuestionable la administración de vitamina K. Más relevante aún es que, gracias a estos conocimientos, se puede comprender el a veces contradictorio riesgo de trombosis en estos pacientes, complicación potencialmente mortal. Palabras claveCoagulación sanguínea, insuficiencia hepática, trombosis, vitamina K. AbstractHepatic insufficiency is a pathology that conditions synthesis and metabolism of various biomolecules. Alterations of hemostasis is one of its first systemic consequences. Because of this and the size of the risks, it is not uncommon for clotting tests to be indispensable for formulating prognostic scales in patients with liver disease.Knowledge about hemostasis has advanced in the last decade, and the classic cascade of activation of coagulation factors has been perfected until it has become the now-current cellular model that considers the valuable and indispensable participation of the endothelium and platelets. Thanks to this, it is possible to understand that the risk of bleeding in patients who have hepatic insufficiency is not only due to deficiencies in production of coagulation factors, and that for this reason administration of vitamin K is questionable. Even more relevant, is the fact that, thanks to this this knowledge, we can understand the sometimes contradictory and potentially life-threatening complication of thrombosis in these patients.

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“…Serotonin is not the only molecule secreted by platelets; the other include ADP, ATP, GDP, pyrophosphate, magnesium and calcium [14]. Platelets acquire serotonin from the plasma by means of the cell membrane serotonin uptake mechanism [15], and store the serotonin in dense granules [14].…”

Section: The Anti-serotonin Approachmentioning

confidence: 99%

Preservation of Haemostasis with Anti-thrombotic Serotonin Antagonism

Mi¹

2017

J Hematol Clin Res

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An enquiry into the lack of attention awarded to serotonin antagonism in the treatment of arterial thrombosis revealed that the mode of action of serotonin and its platelet receptor antagonists was an action upon thrombus growth, and not, as with other anti-platelet drugs upon the initiation of thrombosis. This lack of effect could explain why this approach has been considered not to be effective. However under conditions of arterial stenosis in which there is platelet activation by increased shear stress, and during the growth phase of arterial thrombi, serotonin 5HT 2A antagonism has been demonstrated to have great potentcy in dispersing thrombotic obstruction to blood fl ow. This mode of action, the lack of participation of serotonin in haemostasis, and the absence of serotonin in wounds accounts for the proven lack of effect of effect of pure specifi c 5HT 2A antagonists (i.e., not those with other actions) on operative bleeding and skin bleeding times. This lack of effect on haemostasis solves the dosing problem encountered with other anti-thrombotic drugs, with which drug concentration cannot be controlled with single fi xed doses, leading to the association between increased antithrombotic effi cacy and increased bleeding complications. Thus 5HT 2A antagonism appears to be the preferred approach, from the point of view of safety and lack of bleeding risk; this consideration applies particularly to thrombosis therapy in the context of traumatic accidents, surgical operations and invasive procedures such as angioplasty.

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Platelet secretion: From haemostasis to wound healing and beyond

Cited by 670 publications

References 137 publications

Misshapen/NIK-related kinase (MINK1) is involved in platelet function, hemostasis, and thrombus formation

Misshapen/NIK-related kinase (MINK1) is involved in platelet function, hemostasis, and thrombus formation

Insuficiencia hepática crónica y hemostasia

Preservation of Haemostasis with Anti-thrombotic Serotonin Antagonism

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