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. 2013 Dec 2;8(12):e81595.
doi: 10.1371/journal.pone.0081595. eCollection 2013.

Number and function of bone-marrow derived angiogenic cells and coronary flow reserve in women without obstructive coronary artery disease: a substudy of the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Rajesh Mohandas  1 , Larysa Sautina, Shiyu Li, Xuerong Wen, Tianyao Huo, Eileen Handberg, Yueh-Yun Chi, C Noel Bairey Merz, Carl J Pepine, Mark S Segal
Affiliations

Number and function of bone-marrow derived angiogenic cells and coronary flow reserve in women without obstructive coronary artery disease: a substudy of the NHLBI-sponsored Women's Ischemia Syndrome Evaluation (WISE)

Rajesh Mohandas et al. PLoS One. .

Abstract

Background: In women with ischemia and no obstructive coronary artery disease, the Women's Ischemic Syndrome Evaluation (WISE) observed that microvascular coronary dysfunction (MCD) is the best independent predictor of adverse cardiovascular events. Since coronary microvascular tone is regulated in part by endothelium, we hypothesized that circulating endothelial cells (CEC), which reflect endothelial injury, and the number and function of bone-marrow derived angiogenic cells (BMDAC), which could help repair damaged endothelium, may serve as biomarkers for decreased coronary flow reserve (CFR) and MCD.

Methods: We studied 32 women from the WISE cohort. CFR measurements in response to intracoronary adenosine were taken as an index of MCD. We enumerated BMDAC colonies and CEC in peripheral blood samples. BMDAC function was assessed by assay of migration of CD34+ cells toward SDF-1 and measurement of bioavailable nitric oxide (NO). These findings were compared with a healthy reference group and also entered into a multivariable model with CFR as the dependent variable.

Results: Compared with a healthy reference group, women with MCD had lower numbers of BMDAC colonies [16 (0, 81) vs. 24 (14, 88); P = 0.01] and NO [936 (156, 1875) vs. 1168 (668, 1823); P = 0.02]. Multivariable regression analysis showed strong correlation of CFR to the combination of BMDAC colony count and CD34+ cell function (migration and NO) (R(2) = 0.45; P<0.05).

Conclusions: The BMDAC function and numbers of BMDAC colonies are decreased in symptomatic women with MCD and are independently associated with CFR. These circulating cells may provide mechanistic insights into MCD in women with ischemia.

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Conflict of interest statement

Competing Interests: Dr. Noel Bairey Merz would like to declare that she worked with QMED, Inc., Laurence Harbour, NJ, a commercial funder, in the context of receiving digital Holter monitors free of charge for several of other Women's Ischemic Syndrome Evaluation (WISE) studies. This has no conflict of interest with the content of this paper as no Holters were used in the methods. Further, this does not alter the authors' adherence to all the PLOS ONE policies on sharing data and materials. There are no other conflicts of interest to disclose among any of the investigators.

Figures

Figure 1
Figure 1. Bone-marrow derived angiogenic cell (BMDAC) colonies and intracellular nitric oxide (NO) are reduced in the WISE cohort compared to healthy reference group.
(A and B) Number of circulating endothelial cells and migration ability of CD34+ cells to SDF-1 in the WISE cohort and healthy reference group. (C) Intracellular NO measurement in BMDACs in the WISE cohort and healthy reference group. (D) BMDAC colonies in the WISE cohort and healthy reference group. Horizontal bars indicate the median; upper and lower edges of box are 75th and 25th percentiles. *P<0.05.
Figure 2
Figure 2. The coronary flow reserve (CFR) predicted from the cell variables closely approximates the measured CFR (R2 = 0.45, P<0.05).
See this image and copyright information in PMC

References

    1. Douglas PS, Patel MR, Bailey SR, Dai D, Kaltenbach L, et al. (2011) Hospital variability in the rate of finding obstructive coronary artery disease at elective, diagnostic coronary angiography. J Am Coll Cardiol 58: 801–809. - PubMed
    1. Jespersen L, Hvelplund A, Abildstrom SZ, Pedersen F, Galatius S, et al. (2012) Stable angina pectoris with no obstructive coronary artery disease is associated with increased risks of major adverse cardiovascular events. Eur Heart J 33: 734–744. - PubMed
    1. Gulati M, Cooper-DeHoff RM, McClure C, Johnson BD, Shaw LJ, et al. (2009) Adverse cardiovascular outcomes in women with nonobstructive coronary artery disease: a report from the Women's Ischemia Syndrome Evaluation Study and the St James Women Take Heart Project. Arch Intern Med 169: 843–850. - PMC - PubMed
    1. Merz CN, Kelsey SF, Pepine CJ, Reichek N, Reis SE, et al. (1999) The Women's Ischemia Syndrome Evaluation (WISE) study: protocol design, methodology and feasibility report. J Am Coll Cardiol 33: 1453–1461. - PubMed
    1. Pepine CJ, Anderson RD, Sharaf BL, Reis SE, Smith KM, et al. (2010) Coronary microvascular reactivity to adenosine predicts adverse outcome in women evaluated for suspected ischemia results from the National Heart, Lung and Blood Institute WISE (Women's Ischemia Syndrome Evaluation) study. J Am Coll Cardiol 55: 2825–2832. - PMC - PubMed

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