Open AccessMyocardial Ischemia and Mobilization of Circulating Progenitor Cells
Author(s) -
Hammadah Muhammad,
Samman Tahhan Ayman,
Mheid Ibhar Al,
Wilmot Kobina,
Ramadan Ronnie,
Kindya Bryan R.,
Kelli Heval M.,
O'Neal Wesley T.,
Sandesara Pratik,
Sullivan Samaah,
Almuwaqqat Zakaria,
Obideen Malik,
Abdelhadi Naser,
Alkhoder Ayman,
Pimple Pratik M.,
Levantsevych Oleksiy,
Mohammed Kareem H.,
Weng Lei,
Sperling Laurence S.,
Shah Amit J.,
Sun Yan V.,
Pearce Brad D.,
Kutner Michael,
Ward Laura,
Bremner J. Douglas,
Kim Jinhee,
Waller Edmund K.,
Raggi Paolo,
Sheps David,
Vaccarino Viola,
Quyyumi Arshed A.
Publication year - 2018
Publication title -
journal of the american heart association
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 2.494
H-Index - 85
ISSN - 2047-9980
DOI - 10.1161/jaha.117.007504
Subject(s) - medicine , coronary artery disease , ischemia , cardiology , progenitor cell , chemokine receptor , vascular endothelial growth factor , stromal cell , st segment , chemokine , receptor , myocardial infarction , stem cell , vegf receptors , biology , genetics
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 <0.001) in all patients undergoing exercise stress testing regardless of ischemia. However, the change in stromal‐derived factor‐1α level correlated inversely with the change in 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.