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The Role of Age in Shear-Induced Platelet Activation: A Comparison of Neonatal Cord and Adult Platelets

机译：年龄在剪切诱导的血小板活化中的作用：新生儿脐带和成人血小板的比较

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摘要

The relationship between age and platelet activation is currently not well understood. Experiments have been done evaluation neonatal platelet activation in comparison to adults, and these studies have shown that neonatal platelets are hypoactive when activated via biochemical agonists. In addition, neonatal platelets have shown to have impaired calcium mobilization and release upon activation. Despite these abnormalities, neonatal platelets have shown to aggregate similarly to adult platelets under flow conditions. It is important to note that none of these studies have evaluated neonatal platelet activation with high shear stresses as an agonist. Because of this it is currently not known if neonatal platelets retain their hypoactive properties when activated by a mechanical agonist. Elucidating such a mechanism would provide inside into the role that platelet age plays in shear induced activation, and this knowledge can potentially be translated into the development of new therapeutics to replace the harsh anticoagulants that cardiovascular disease patients take.;The overall goal of this thesis was to provide an exploratory study into the role that age plays in shear induced platelet activation. This was done by comparing thrombin generation, platelet surface marker expression, and activation due to the inhibition of intracellular and extracellular calcium in adult and neonatal cord platelets under high shear conditions. The results from these studies show that neonatal and adult platelets have similar thrombin generation under various shear conditions. Differences observed between neonatal cord and adult platelet Annexin V binding under high shear conditions may suggest a difference in the platelet membrane sensitivity of neonatal platelets when compared to the control. In addition, it was showed the chelation of intracellular calcium and the removal of extracellular calcium do not affect neonatal or adult platelet thrombin generation or Annexin V expression under high shear conditions.
机译：年龄与血小板活化之间的关系目前尚不清楚。已经进行了与成人相比评估新生儿血小板活化的实验，这些研究表明，当通过生化激动剂活化时，新生儿血小板活性低下。此外，新生儿血小板已显示出钙动员受损并在激活后释放。尽管有这些异常，但在流动条件下，新生儿血小板的聚集与成人血小板相似。重要的是要注意，这些研究都没有评估以高剪切应力作为激动剂的新生儿血小板活化。因此，目前尚不清楚新生儿血小板在被机械激动剂激活时是否保持其活性不足。阐明这种机制将使血小板年龄在剪切诱导的激活中发挥作用，并且这一知识可能会转化为开发新的疗法以替代心血管疾病患者服用的强效抗凝剂。；本论文的总体目标该研究旨在探索年龄在剪切诱导的血小板活化中所起的作用。通过比较凝血酶的生成，血小板表面标志物的表达以及在高剪切条件下成年和新生儿脐带血血小板中细胞内和细胞外钙的抑制所引起的活化来完成这项工作。这些研究的结果表明，在各种剪切条件下，新生儿和成人血小板具有相似的凝血酶生成能力。在高剪切条件下观察到的新生儿脐带和成人血小板膜联蛋白V结合之间的差异可能表明与对照组相比，新生儿血小板的血小板膜敏感性有所差异。此外，研究表明在高剪切条件下，细胞内钙的螯合和细胞外钙的去除不会影响新生儿或成人血小板凝血酶的产生或膜联蛋白V的表达。

著录项

  • 作者

    Zigomalas, Amanda Marie.;

  • 作者单位

    State University of New York at Stony Brook.;

  • 授予单位 State University of New York at Stony Brook.;
  • 学科 Biomedical engineering.;Bioengineering.;Biomechanics.
  • 学位 M.S.
  • 年度 2018
  • 页码 52 p.
  • 总页数 52
  • 原文格式 PDF
  • 正文语种 eng
  • 中图分类
  • 关键词

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