CXCR4+ and FLK-1+ identify circulating cells associated with improved cardiac function in patients following myocardial infarction.
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.
Mayo Medical School, College of Medicine, Rochester, MN, USA.
Rahul
R
Suresh
Anca
A
Chiriac
Kashish
K
Goel
Hector R
HR
Villarraga
Francisco
F
Lopez-Jimenez
Randal J
RJ
Thomas
Andre
A
Terzic
Timothy J
TJ
Nelson
Carmen
C
Perez-Terzic
D000328:Adult; D000368:Aged; D015415:Biomarkers / Q000097:blood; D016022:Case-Control Studies; D002452:Cell Count; D005260:Female; D005434:Flow Cytometry; D006801:Humans; D017493:Leukocyte Common Antigens / Q000097:blood; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood* / Q000276:immunology / Q000473:pathology / Q000503:physiopathology; D011237:Predictive Value of Tests; D011379:Prognosis; D019718:Receptors, CXCR4 / Q000097:blood*; D020127:Recovery of Function; D013234:Stem Cells / Q000276:immunology / Q000378:metabolism* / Q000473:pathology; D013318:Stroke Volume; D013599:Systole; D013997:Time Factors; D015854:Up-Regulation; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000097:blood*; D016277:Ventricular Function, Left
D015415:Biomarkers; C527276:CXCR4 protein, human; D019718:Receptors, CXCR4; D040301:Vascular Endothelial Growth Factor Receptor-2; D017493:Leukocyte Common Antigens; C516769:PTPRC protein, human