OC 58.5 Cooperation between Platelet β1 and β3 Integrins in the Arrest of Bleeding Under Inflammatory Conditions in Mice

ceramides 18:1/16:0 and 18:1/18:0, which are positively correlated with platelet hyperresponsiveness to multiple agonists and heightened thrombus formation in aged mice.Employing Mfsd2b-siRNA, we reveal that MkPs contribute to reduced expression of cellular senescence markers γ-H2A.X (telomere shortening) and p53 (cell cycle arrest), and caspase-3 (apoptosis), and increased expression of Sirt1, which is known to delay cellular senescence and rejuvenate aged cells. Conclusion(s):Our studies demonstrated that aging affects Mfsd2b expression in specific MkP subpopulations that regulate circulating S1P and ceramides.These findings indicate that modulation of sphingolipids and ceramides by deletion of Mfsd2b strongly regulates aging-related platelet hyperreactivity and thrombus formation, which suggests that targeting Mfsd2b in specific MkP subpopulations could contribute to important clues to future personalized medicine for the prevention of thrombotic disorders in aging.