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Circulating CD34+ cell subsets in patients with coronary endothelial dysfunction

Nature Clinical Practice Cardiovascular Medicine volume 5, pages 489–496 (2008)Cite this article

Abstract

Background Endothelial dysfunction is an early manifestation of atherosclerotic disease. Circulating cells that express CD34, including endothelial and hematopoietic progenitor cells, might play a part in the development and progression of atherosclerosis. The aim of this study was to evaluate the association between coronary endothelial dysfunction and concentrations of circulating CD34+ cell subsets.

Methods Intracoronary acetylcholine challenge was used to test for coronary endothelial dysfunction in 57 consecutive patients scheduled to undergo diagnostic coronary angiography and with no signs of substantial obstructive lesions. Mononuclear cells were extracted from whole blood samples taken from all patients, analyzed by flow cytometry for CD14, CD34, CD133, CD45, and vascular endothelial growth factor receptor 2 (VEGFR2), and cultured for functional analysis.

Results Compared with patients with normal coronary endothelial function, in those with coronary endothelial dysfunction, the number of circulating CD34+/CD45dim/VEGFR2− cells, CD34+/CD45dim/CD133+/VEGFR2− cells and colony-forming units were reduced. Concentrations of CD34+/CD45−/VEGFR2+ cells did not differ between groups.

Conclusions Regulation of CD34+ cell subsets seems to differ between patients with coronary endothelial dysfunction and those with normal coronary endothelial function. Changes in specific circulating progenitor cell subsets might, therefore, be an early manifestation of atherosclerosis.

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Figure 1: Hematopoietic progenitor cell counts, calculated according to the International Society of Hematotherapy and Graft Engineering criteria.
Figure 2: Enumeration strategy for endothelial progenitor cell counts.
Figure 3: Numbers of CD34+/CD45dim/VEGFR2− and CD34+/CD45−/VEGFR2+ cells counted by flow cytometry from whole blood samples.
Figure 4: Numbers of CD34+/CD45dim/VEGFR2−, CD34+/CD45dim/CD133+/VEGFR2−, and CD34+/VEGFR2+/CD45− cells counted by flow cytometry from buffy coat from 19 patients, with and without CED.
Figure 5: Colony forming units in patients with and without coronary endothelial dysfunction.

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Acknowledgements

This study was funded by the National Institutes of Health (HL76611, 75566) and the Minnesota Partnership for Biotechnology and Medical Genomics. Special thanks are given to JE Tarara and staff at the Mayo Clinic Flow Cytometry Core Facility for their assistance with processing the samples, to T Hoskin and D Schroeder for biostatistical advice, and to ME Crouch for her secretarial support.

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  1. Division of Cardiovascular Diseases, Mayo Clinic, Rochester, 55905, MN, USA

    Barry A Boilson, Thomas J Kiernan, Adriana Harbuzariu, Rebecca E Nelson, Amir Lerman & Robert D Simari

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Correspondence to Robert D Simari.

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Boilson, B., Kiernan, T., Harbuzariu, A. et al. Circulating CD34+ cell subsets in patients with coronary endothelial dysfunction. Nat Rev Cardiol 5, 489–496 (2008). https://doi.org/10.1038/ncpcardio1277

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