Relative survival potential of platelets is associated with platelet CXCR4/CXCR7 surface exposure and functional recovery following STEMI

Abstract

Background and aimsPlatelets are critically involved in tissue repair and regeneration, which depend on their inflammatory properties and survival. SDF-1 ligates to CXCR4 and CXCR7 and contributes to the regulation of platelet survival. Platelet CXCR4/CXCR7 are involved in myocardial regeneration after infarction and are associated with outcomes in patients with symptomatic coronary artery disease. This study investigates the CXCR4/CXCR7 platelet survival axis ex vivo. Methods87 patients with ST-segment elevation myocardial infarction (STEMI) were included and analyzed for platelet surface exposure of CXCR4, CXCR7, Annexin V binding and tetramethylrhodamine ethyl ester (TMRE) response. Serum of 38 patients was analyzed for FasL, TNFα, TNF RI, TNF RII and TRAIL with Bioplex®. The majority of patients received sequential cardiac MRI (intrahospital, 6-month follow-up). ResultsWe found a strong and positive correlation between surface exposure of CXCR4 and CXCR7 (ρ = 0.856, p<0.001). Relative survival potential correlated significantly with both platelet surface exposure of CXCR4 and CXCR7 (ρ = 0.365, p = 0.019; ρ = 0.417, p = 0.006) and furthermore with improvement of myocardial left ventricular ejection fraction (LVEF) (ρ = 0.490, p = 0.013). High relative survival potential showed significantly higher levels for both CXCR4 and CXCR7 surface exposure (MFI 87.3 vs. 69.0, p = 0.037; MFI 71.4 vs. 59.3, p = 0.045). We found a significant change in absolute LVEF% over the course of 6 months in patients with high CXCR7 platelet surface exposure (LVEF% 44.3 vs. 60.0, p≤0.001). ConclusionsPlatelet survival is associated with platelet surface exposure of CXCR4 and CXCR7 in STEMI patients and contributes to functional recovery after STEMI.