CXCR4+ and FLK-1+ Identify Circulating Cells Associated with Improved Cardiac Function in Patients Following Myocardial Infarction

Abstract

The biomarkers CXCR4/FLK-1 select cardiac progenitors from a stem cell pool in experimental models. However, the translational value of these cells in human ischemic heart disease is unknown. Here, flow-cytometry identified CD45(-)/CXCR4(+)/FLK-1(+) cells in 30 individuals without ischemic heart disease and 33 first-time acute myocardial infarction (AMI) patients. AMI patients had higher CD45(-)/CXCR4(+)/FLK-1(+) cell-load at 48-h and 3- and 6-months post-AMI (p = 0.003,0.04,0.04, respectively) than controls. Cardiovascular risk factors and left ventricular (LV) ejection fraction were not associated with cell-load. 2D-speckle-tracking strain echocardiography assessment of LV systolic function showed improvement in longitudinal strain and dyssynchrony during follow-up associated with longitudinal increases in and higher 48-h post-AMI CD45(-)/CXCR4(+)/FLK-1(+) cell-load (r = -0.525, p = 0.025; r = -0.457, p = 0.029, respectively). In conclusion, CD45(-)/CXCR4(+)/FLK-1(+) cells are present in adult human circulation, increased in AMI and associated with improved LV systolic function. Thus, CD45(-)/CXCR4(+)/FLK-1(+) cells may provide a diagnostic tool to follow cardiac regenerative capacity and potentially serve as a prognostic marker in AMI.