TY - JOUR
T1 - Myocardial ischemia and mobilization of circulating progenitor cells
AU - Hammadah, Muhammad
AU - Tahhan, Ayman Samman
AU - Al Mheid, Ibhar
AU - Wilmot, Kobina
AU - Ramadan, Ronnie
AU - Kindya, Bryan R.
AU - Kelli, Heval M.
AU - O'Neal, Wesely T.
AU - Sandesara, Pratik
AU - Sullivan, Samaah
AU - Almuwaqqat, Zakaria
AU - Obideen, Malik
AU - Abdelhadi, Naser
AU - Alkhoder, Ayman
AU - Pimple, Pratik M.
AU - Levantsevych, Oleksiy
AU - Mohammed, Kareem H.
AU - Weng, Lei
AU - Sperling, Laurence S.
AU - Shah, Amit J.
AU - Sun, Yan V.
AU - Pearce, Brad D.
AU - Kutner, Michael
AU - Ward, Laura
AU - Douglas Bremner, J.
AU - Kim, Jinhee
AU - Waller, Edmund K.
AU - Raggi, Paolo
AU - Sheps, David
AU - Vaccarino, Viola
AU - Quyyumi, Arshed A.
N1 - Publisher Copyright:
© 2018 The Authors.
PY - 2018/2/1
Y1 - 2018/2/1
N2 - 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%). CD34+ and CD34+/chemokine (C-X-C motif) receptor 4 PCs 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 ExMI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with ExMI had a significant decrease in CD34+/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 ExMI had an increase in CD34+/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 ExMI (P = 0.03), suggesting a greater decrease in PCs in those with a greater change in stromal-derived factor- 1α level with exercise. Conclusions--ExMI is associated with a significant decrease in circulating levels of CD34+/chemokine (C-X-C motif) receptor 4 PCs, likely attributable, at least in part, to stromal-derived factor-1α-mediated homing of PCs to the ischemic myocardium. The physiologic consequences of this uptake of PCs and their therapeutic implications need further investigation.
AB - 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%). CD34+ and CD34+/chemokine (C-X-C motif) receptor 4 PCs 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 ExMI was 31% and 41% during exercise and pharmacological stress testing, respectively. Patients with ExMI had a significant decrease in CD34+/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 ExMI had an increase in CD34+/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 ExMI (P = 0.03), suggesting a greater decrease in PCs in those with a greater change in stromal-derived factor- 1α level with exercise. Conclusions--ExMI is associated with a significant decrease in circulating levels of CD34+/chemokine (C-X-C motif) receptor 4 PCs, likely attributable, at least in part, to stromal-derived factor-1α-mediated homing of PCs to the ischemic myocardium. The physiologic consequences of this uptake of PCs and their therapeutic implications need further investigation.
KW - Coexpression of chemokine receptor 4
KW - Ischemia
KW - Progenitor cell
KW - Stromal-derived factor
KW - Vascular endothelial growth factor
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U2 - 10.1161/JAHA.117.007504
DO - 10.1161/JAHA.117.007504
M3 - Article
C2 - 31898922
AN - SCOPUS:85042145371
SN - 2047-9980
VL - 7
JO - Journal of the American Heart Association
JF - Journal of the American Heart Association
IS - 4
M1 - e007504
ER -