Abstract 150: Hypoxia and Ischemia Promote a Maladaptive Platelet Phenotype

Background: An understudied area of platelet biology is that ischemic diseases such as peripheral vascular disease (PVD) can alter the platelet phenotype, and this may lead to unpredictable effects of anti-platelet agents. Methods: Isolated murine and human platelets were exposed to a reduced oxygen environment (hypoxia chamber, 5% O2). Platelet activation was assessed as mean fluorescence intensity (MFI) of surface p-selectin by flow cytometry, and morphologic changes by confocal microscopy. A murine model of critical limb ischemia (CLI) was used to assess changes in platelet activity in wild-type (WT) and in platelet ERK5-/- mice. Limb blood flow was assessed by laser Doppler imaging. Hypoxia was additionally examined in mice by unilateral pneumonectomy. Western blotting was used to assess protein expression. Results: In human platelets ex vivo at 5% O2, platelet activation increased to 5076 MFI±409 from 3548 MFI±187 at 20% O2 (P=0.005). With the ERK5 inhibitor XMD892, platelet activation at 5% O2decrea...