Flow dynamics and haemostasis

Mario Mazzucato, Andrea Santomaso, Paolo Canu, Zaverio M. Ruggeri, Luigi De Marco

Research output: Contribution to journalArticlepeer-review

Abstract

Summary. Fluid-dynamic conditions that are compatible with tensile stress on the bonds between platelet glycoprotein Ibα and immobilized von Willebrand factor A1 domain (VWF-A1) led to Ca++ release from intracellular stores (type α/β peaks), which preceded stationary platelet adhesion. Raised levels of cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate inhibited these [Ca++]i oscillations and prevented stable adhesion. Once adhesion was established through the integrin αIIbβ3 new [Ca++]i oscillations (type γ) of greater amplitude and duration, and involving a transmembrane ion flux, developed in association with the recruitment of additional platelets into aggregates. We have defined the distinct roles that the two ADP receptors, P2Y1 and P2Y12, play in the early events that follow the initial platelet interaction with immobilized VWF-A1 under high flow conditions. We have examined the consequences of specific pharmacologic inhibition of P2 receptors and our findings demonstrate a differential role of P2Y1, and P2Y12, respectively, in platelet adhesion and aggregation onto immobilized VWF under elevated shear stress, and highlight the distinct contribution of signaling pathways dependent on Src family kinases, PLC, and phosphoinositide 3-kinase (PI 3-K) to these processes. Results have been achieved through original experiments under flow, thoroughly characterized by ad hoc image analysis techniques and quantitative kinetic analysis.

Original languageEnglish
Pages (from-to)130-138
Number of pages9
JournalAnnali dell'Istituto Superiore di Sanita
Volume43
Issue number2
Publication statusPublished - 2007

Keywords

  • Adhesion equilibrium constant
  • ADP receptors
  • Image analysis
  • Platelets
  • Signaling
  • von Willebrand factor

ASJC Scopus subject areas

  • Public Health, Environmental and Occupational Health

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