Abstract 17918: Platelet Depletion Exacerbates Myocardial Injury Through Decreasing Stem Cell Mobilization and S1P Concentration Following Myocardial Infarction
Introduction: Myocardial infarction (MI) and its associated complications are the leading cause of morbidity and mortality in the United States. Platelets play a major role in homeostasis and wound healing, however, their role in myocardial recovery after injury is not understood.
Hypothesis: Platelets provide important signaling molecules such as sphingosine-1 phosphate and cytokines that play a major role in cardiac recovery. Depleting platelets after MI is expected to result in reduced cardiac recovery.
Methods: Mice were randomized into platelet depleted group using monoclonal antibodies and control group using isotype controls. MI surgery was performed using LAD ligation and mice were sacrificed at 7 and 30 days for histological examination. Additionally, cardiac function was assessed using echocardiography at 35 days after MI.
Results: Platelet depletion was associated with reduction in cardiac function at 35 days post-MI compared to control mice. Global left ventricular ejection fraction, fractional shortening, infarct wall thickness and left ventricular mass were lower in platelet depleted mice compared to controls. Scar size, as assessed by mason trichrome staining, was larger in platelet depleted mice. Mechanistically, plasma level of sphoingosine-1 phosphate (S1P), a major survival and stem cell mobilizing factor, was reduced in platelet depleted mice. Reduction in S1P in platelet depleted mice was associated with higher numbers of apoptotic cells as assessed by Caspace 3 staining. Peripheral blood count of mobilized stem cells, as assessed by flow cytometry, was reduced at day 5 after MI in platelet depleted mice compared to controls.
Conclusion: Platelets play a major role in cardiomyocyte survival and cardiac recovery after ischemic injury. The salutary effects of platelets are mediated, at least in part, by S1P signaling and anti-apoptotic effects.
Author Disclosures: A. Idris: None. S. Ye: None. H. Tripathi: None. A. Abdel-Latif: None.
- © 2016 by American Heart Association, Inc.