Myocardial Ischemia and Mobilization of Circulating Progenitor Cells

Background The response of progenitor cells (PCs) to transient myocardial ischemia in patients with coronary artery disease remains unknown. We aimed to investigate the PC response to exercise‐induced myocardial ischemia (ExMI) and compare it to flow mismatch during pharmacological stress testing. Methods and Results A total of 356 patients with stable coronary artery disease underwent 99mTc‐sestamibi myocardial perfusion imaging during exercise (69%) or pharmacological stress (31%). CD 34 + and CD 34 + /chemokine (C‐X‐C motif) receptor 4 PC s were enumerated by flow cytometry. Change in PC count was compared between patients with and without myocardial ischemia using linear regression models. Vascular endothelial growth factor and stromal‐derived factor‐1α were quantified. Mean age was 63±9 years; 76% were men. The incidence of Ex MI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with Ex MI had a significant decrease in CD 34 + /chemokine (C‐X‐C motif) receptor 4 (−18%, P =0.01) after stress that was inversely correlated with the magnitude of ischemia ( r =−0.19, P =0.003). In contrast, patients without Ex MI had an increase in CD 34 + /chemokine (C‐X‐C motif) receptor 4 (14.7%, P =0.02), and those undergoing pharmacological stress had no change. Plasma vascular endothelial growth factor levels increased (15%, P PC counts in those with Ex MI ( P =0.03), suggesting a greater decrease in PC s in those with a greater change in stromal‐derived factor‐1α level with exercise. Conclusions Ex MI is associated with a significant decrease in circulating levels of CD 34 + /chemokine (C‐X‐C motif) receptor 4 PC s, likely attributable, at least in part, to stromal‐derived factor‐1α–mediated homing of PC s to the ischemic myocardium. The physiologic consequences of this uptake of PC s and their therapeutic implications need further investigation.