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Multicenter Study
. 2016 Oct:253:111-117.
doi: 10.1016/j.atherosclerosis.2016.08.026. Epub 2016 Aug 26.

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

Girum Mekonnen  1 , Salim S Hayek  1 , Puja K Mehta  2 , Qunna Li  1 , Ernestine Mahar  1 , Liping Mou  1 , Tanya S Kenkre  3 , John W Petersen  4 , Babak Azarbal  2 , Bruce Samuels  2 , R David Anderson  4 , Tara Sedlak  5 , Melody Zaya  2 , Megha Agarwal  2 , Afsaneh Haftbaradaran  2 , Margo Minissian  2 , Eileen Handberg  4 , Carl J Pepine  4 , Christopher R Cogle  4 , C Noel Bairey Merz  2 , Edmund K Waller  1 , Arshed A Quyyumi  6
Affiliations
Multicenter Study

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

Girum Mekonnen et al. Atherosclerosis. 2016 Oct.

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.

Keywords: Circulating progenitor cells; Coronary flow reserve; Microvascular function.

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Conflict of interest statement

Conflict of interest

GM is supported by a grant from the National Heart, Lung, and Blood Institute of the National Institutes of Health (P01HL101398). PKM: Gilead Research Grant; CJP: WISE Grant from NHLBI, CNBM: Honoraria from Annual DeStevens Lectureship, 24th Annual Dan May Lectureship, California Society for Cardiac Rehabilitation, NIHSEP, and ACC-SAP. All other authors have no disclosures.

Figures

Fig. 1.
Fig. 1.. Flow cytometric analysis of progenitor cell counts.
Representative flow-cytometric analysis of peripheral blood stained with monoclonal antibodies against human fluorescein isothiocyanate (FITC)-labeledCD34, peridinin chlorophyII protein (PerCP)-labeled CD45, allophycocyanin (APC)-labeled CD133, phycoerythrin (PE)-labeled VEGFR-2 and phycoerythrin-cyanine 7 (PE-Cy7)-labeled CXCR4. First, mononuclear cells (MNC) were gated on a forward scatter (FSC) vs. side scatter (SSC) (A). Second, CD34+ cells were gated within MNC gate (B). CD45dim cells were selected within CD34+ gate. Last, CD133, VEGFR2 and CXCR4 expression was gated within CD34 + CD45dim gate (D, E, F).
Fig. 2.
Fig. 2.. Progenitor cells and coronary flow reserve.
Relationship between log-transformed (base 2) circulating progenitor cell counts and coronary flow reserve (CFR). The scatterplots depict correlations between CFR and (A) CD34+, (B) CD34+/CD133+, (C) CD34+/CXCR4+ and (D) CD34+/VEGFR2+ cells. Pearson correlations and associated p-values are displayed.
See this image and copyright information in PMC

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