Mice without the protein PKC-alpha exhibited diminished thrombus formation in vivo but also showed no evidence of overt bleeding, according to investigators at the University of Bristol. They found that PKC-alpha has a major role?in inside-out regulation of bleeding but no significant role in outside-in signaling.
The ablation of in vitro thrombus formation in certain platelets was rescued by the addition of ADP, consistent with the key mechanistic finding that dense-granule biogenesis and secretion depend upon PKC-alpha expression. Furthermore, defective platelet aggregation in response to either collagen-related peptide or thrombin could be overcome by an increase in agonist concentration. Evidence of overt bleeding including gastrointestinal and tail bleeding was not seen in these mice.
The researchers thus conclude that the effects of PKC-alpha?ablation on thrombus formation and granule secretion may implicate PKC-alpha??as a drug target for antithrombotic therapy. This article appears online January 19 in the Journal of Clinical Investigation.