Myocardial Ischemia and Mobilization of Circulating Progenitor Cells

• Type of Material: Article
• Authors: Muhammad Hammadah, Emory University; Ayman Samman Tahhan, Emory University; Ibhar Al Mheid, Emory University; Kobina Wilmot, Emory University; Ronnie Ramadan, Emory University; Bryan R. Kindya, Emory University; Heval M. Kelli, Emory University; Wesley T. O'Neal, Emory University; Pratik Sandesara, Emory University; Samaah Sullivan, Emory University; Zakaria Almuwaqqat, Emory University; Malik Obideen, Emory University; Naser Abdelhadi, Emory University; Ayman Alkhoder, Emory University; Pratik M. Pimple, Emory University; Oleksiy Levantsevych, Emory University; Kareem H. Mohammed, Emory University; Lei Weng, Emory University; Laurence S Sperling, Emory University; Amit J. Shah, Emory University; Yan Sun, Emory University; Brad Pearce, Emory University; Michael Kutner, Emory University; Laura Ward, Emory University; J. Douglas Bremner, Emory University; Jinhee Kim, Emory University; Edmund K Waller, Emory University; Paolo Raggi, Emory University; David Sheps, University of Florida; Viola Vaccarino, Emory University; Arshed Ali Quyyumi, Emory University
• Language: English
• Date: 2018-02-20
• Publisher: Wiley Open Access: Creative Commons Attribution Non-Commercial
• Publication Version: Final Published Version
• Copyright Statement: © 2018 The Authors.
• License: Creative Commons Attribution-NonCommercial 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1161/JAHA.117.007504
• Title of Journal or Parent Work: Journal of the American Heart Association
• ISSN: 2047-9980
• Volume: 7
• Issue: 4
• Grant/Funding Information: This work was supported by the NIH (P01 HL101398, P20HL113451‐01, P01HL086773‐06A1, R56HL126558‐01, R01 HL109413, R01HL109413‐02S1, UL1TR000454, KL2TR000455, K24HL077506, and K24 MH076955).; Kelli and Sullivan have been supported by National Heart, Lung, and Blood Institute T32 grant THL130025A.; Kelli and Tahhan have been supported by the Abraham J. and Phyllis Katz Foundation.; O'Neal has been supported by American Heart Association grant F32HL134290.
• Keywords: coexpression of chemokine receptor 4; CORONARY-ARTERY-DISEASE; ischemia; ENDOTHELIAL-CELLS; stromal-derived factor; CHRONIC HEART-FAILURE; STEM-CELLS; Cardiac & Cardiovascular Systems; Life Sciences & Biomedicine; Cardiovascular System & Cardiology; CARDIOVASCULAR RISK; progenitor cell; Science & Technology; BONE-MARROW; vascular endothelial growth factor; TRAINING INCREASES; INFARCTED HUMAN MYOCARDIUM; ANGIOGENIC CELLS; SIGNALING PATHWAY
• Research Categories: Biology, Biostatistics; Health Sciences, Medicine and Surgery; Health Sciences, Oncology; Health Sciences, Epidemiology; Psychology, Behavioral; Health Sciences, Public Health; Biology, Bioinformatics

Abstract

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.