Manipulation of the Angiogenic Balance by Pharmacological Inhibition of Platelet PKC Signalling

  • Author / Creator
    Moncada de la Rosa,Cesar A.
  • Blood platelets mediate wound healing by preventing bleeding and by supporting growth of new blood vessels. Blood vessel growth is supported in part by growth factors released from platelet α-granules. Both platelet aggregation and α-granule release are mediated by intracellular signaling pathways via distinct protein kinase C (PKC) isoforms. Recent evidence suggests that the conventional PKC isoforms α and β are respectively responsible for signaling α-granule release and aggregation. We hypothesized that titration of platelets with conventional PKC (cPKC) inhibitors will have differential effects on aggregation and the release of angiogenic factors from α-granules. Our results indicate that careful titration of cPKC inhibitors preferentially prevents the release of the pro-angiogenic factor VEGF but not the anti-angiogenic factor TSP-1 from platelet α-granules. Also inhibition of VEGF release from α-granules may occur independent of platelet aggregation. Hence, we have been able to uncouple angiogenesis-promoter from aggregation-stimulator abilities of platelets.

  • Subjects / Keywords
  • Graduation date
  • Type of Item
  • Degree
    Master of Science
  • DOI
  • License
    This thesis is made available by the University of Alberta Libraries with permission of the copyright owner solely for non-commercial purposes. This thesis, or any portion thereof, may not otherwise be copied or reproduced without the written consent of the copyright owner, except to the extent permitted by Canadian copyright law.
  • Language
  • Institution
    University of Alberta
  • Degree level
  • Department
    • Faculty of Pharmacy and Pharmaceutical Sciences
  • Supervisor / co-supervisor and their department(s)
    • Jurasz, Paul (Pharmacy and Pharmaceutical Sciences)
  • Examining committee members and their departments
    • Cheung, Po-Yin (Pharmacology)
    • Siraki, Arno (Pharmacy and Pharmaceutical Sciences)
    • Seubert, John (Pharmacy and Pharmaceutical Sciences)