Circulating progenitor cells and coronary microvascular dysfunction: Results from the NHLBI-sponsored Women's Ischemia Syndrome Evaluation - Coronary Vascular Dysfunction Study (WISE-CVD)

• Type of Material: Article
• Authors: Girum Mekonnen, Emory University; Salim S Hayek, Emory University; Puja Mehta, Emory University; Qunna Li, Emory University; Ernestine Mahar, Emory University; Liping Mou, Emory University; Tanya S Kenkre, University of Pittsburgh; John W Petersen, University of Florida; Babak Azarbal, Cedars-Sinai Heart Institute; Bruce Samuels, Cedars-Sinai Heart Institute; David R Anderson, University of Florida; Tara Sedlak, University of British Columbia; Melody Zaya, Cedars-Sinai Heart Institute; Megha Agarwal, Cedars-Sinai Heart Institute; Afsaneh Haftbaradaran, Cedars-Sinai Heart Institute; Margo Minissian, Cedars-Sinai Heart Institute; Eileen Handberg, University of Florida; Carl J Pepine, University of Florida; Christopher R Cogle, University of Florida; Noel Bairey C Merz, Cedars Sinai Heart Inst; Edmund Waller, Emory University; Arshed Quyyumi, Emory University
• Language: English
• Date: 2016-10-01
• Publisher: ELSEVIER IRELAND LTD
• Publication Version: Author Accepted Manuscript (After Peer Review)
• Copyright Statement: © 2016 Elsevier Ireland Ltd. All rights reserved.
• License: Creative Commons Attribution-NonCommercial-NoDerivs 4.0 International
• Final Published Version (URL): http://dx.doi.org/10.1016/j.atherosclerosis.2016.08.026
• Title of Journal or Parent Work: ATHEROSCLEROSIS
• Volume: 253
• Start Page: 111
• End Page: 117
• Grant/Funding Information: This work was supported by contracts from the National Heart, Lung and Blood Institutes, nos. N01-HV-68161, N01-HV-68162, N01-HV-68163, N01-HV-68164, K23HL105787, grants U0164829, U01 HL649141, U01 HL649241, T32HL69751, R01-HL090957, 1R03AG032631 from the National Institute on Aging, GCRC grant MO1-RR00425 from the National Center for Research Resources and grants from the Gustavus and Louis Pfeiffer Research Foundation, Danville, NJ, The Women’s Guild of Cedars-Sinai Medical Center, Los Angeles, CA, The Ladies Hospital Aid Society of Western Pennsylvania, Pittsburgh, PA, and QMED, Inc., Laurence Harbor, NJ, the Edythe L. Broad Women’s Heart Research Fellowship, Cedars-Sinai Medical Center, Los Angeles, California, the Barbra Streisand Women’s Cardiovascular Research and Education Program, Cedars-Sinai Medical Center, Los Angeles, The Society for Women’s Health Research (SWHR), Washington, D.C., and the Linda Joy Pollin Women’s Heart Health Program.
• Keywords: Cardiovascular System & Cardiology; POPULATION; HEMATOPOIETIC STEM; Science & Technology; MOBILIZATION; Life Sciences & Biomedicine; Coronary flow reserve; CARDIOVASCULAR OUTCOMES; Circulating progenitor cells; Peripheral Vascular Disease; Microvascular function; CD34(+) CELLS; INCREASES; HEART-DISEASE; RISK-FACTORS; NUMBER; PERIPHERAL-BLOOD; Cardiac & Cardiovascular Systems

Abstract

Background and aims Ischemia stimulates a reparative response resulting in mobilization of circulating progenitor cells (CPCs). We hypothesized that women with chronic myocardial ischemia from coronary microvascular disease (CMD) will mobilize CPCs. Methods In 123 women with ischemic symptoms and signs but no obstructive coronary artery disease (CAD) enrolled in the Women's Ischemia Syndrome Evaluation – Coronary Vascular Dysfunction Study (WISE-CVD), we measured coronary flow reserve (CFR) in response to intracoronary adenosine. Peripheral blood CPCs were measured using flow cytometry for expression of CD34, CD133, CXCR4, and VEGFR2. Results Subjects were 53 ± 11 years, BMI 30 ± 8; 44% hypertensive, 11% diabetic, 23% hyperlipidemic and 7% smokers. Lower CFR correlated inversely with higher levels of hematopoietic-enriched CD34+ (r = −0.23, p = 0.011), CD34+/CD133+ (r = −0.24, p = 0.008), and CD34+/CXCR4+ (r = −0.19, p = 0.036) cells. In multivariable regression analyses, after adjusting for traditional cardiovascular risk factors, lower CFR remained significantly associated with elevated levels of CD34+ (β −0.18, p = 0.042), CD34+/CD133+ (β −0.24, p = 0.036), and CD34+/CXCR4+ (β −0.22, p = 0.050) cells. We found no association between CFR and CD34+/VEGFR2+ cells. Conclusions In women with non-obstructive CAD, impaired CFR is associated with higher levels of CPCs, suggesting that chronic myocardial ischemia from CMD stimulates CPC mobilization. The functional significance of elevated CPCs in these subjects requires further investigation as a potential biomarker and treatment target.