CORRESPONDENCE: LETTER TO THE EDITOR
Reply
Daniel C. Link, MD* and
Richard G. Bach, MD
* Washington University, Division of Oncology, 660 South Euclid, Campus Box 8007, Saint Louis, Missouri 63110 (Email: dlink{at}im.wustl.edu).
We would like to thank Dr. Fadini and colleagues for their comments regarding our study (1) recently published in JACC. Dr. Fadini et al. point out that our data, which shows that the numbers of endothelial progenitor cells (EPCs) and circulating angiogenic cells (CACs) in the blood of patients referred for cardiac catheterization are increased in those patients with angiographically significant coronary artery disease (CAD), differs from the results of some previously published studies. We agree. But as discussed in our study and highlighted by Drs. Leor and Marber in an accompanying editorial in JACC (2), it is critical when comparing different studies that the type of circulating angiogenic cells be precisely defined. Indeed, a recent study by Yoder et al. (3) suggested that culture techniques commonly used to quantify EPCs actually measure myeloid progenitor cells (3). In our study, we used rigorous histological and flow cytometry techniques to quantify EPCs and CACs (not simply a longer culture method, as suggested by Dr. Fadini et al.). Furthermore, whereas we compared these cell numbers to angiographically defined CAD among patients across a wide spectrum of disease severity, many previous studies identified atherosclerotic disease or its absence noninvasively, which may seriously limit sensitivity and specificity. We agree that a more precise definition of atherosclerosis by, for example, use of intravascular ultrasound, may add to our understanding of the relationship between the different EPC subsets and CAD.
From our observations, we speculated that significant myocardial ischemia may be a proximal determinant of EPC number in the peripheral blood. Dr. Fadini et al. question this, but in support of their opinion they wrongly state that patients with actual myocardial ischemia were excluded from our study. Although patients with acute myocardial infarction and unstable angina were excluded from our investigation, the majority of our patients with significant CAD were symptomatic (and anginal symptoms likely underestimate the frequency of true myocardial ischemia). Importantly, we observed the highest numbers of circulating EPCs and CACs in patients selected clinically to require revascularization. Of relevance, previous studies have shown an increase in circulating EPCs in patients with unstable angina (4) or acutely in response to exercise-induced ischemia (5), observations that appear consistent with the hypothesis that ischemia may be an important factor for the number of circulating EPCs.
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References
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- Güven H, Shepherd RM, Bach RG, Capoccia BJ, Link DC. The number of endothelial progenitor cell colonies in the blood is increased in patients with angiographically significant coronary artery disease J Am Coll Cardiol 2006;48:1579-1587.[Abstract/Free Full Text]
- Leor J, Marber M. Endothelial progenitors: a new Tower of Babel? J Am Coll Cardiol 2006;48:1588-1590.[Free Full Text]
- Yoder MC, Mead LE, Prater D, et al. Re-defining endothelial progenitor cells via clonal analysis and hematopoietic stem/progenitor cell principals Blood 2006Oct 19; [E-pub ahead of print].
- George J, Goldstein E, Abashidze S, et al. Circulating endothelial progenitor cells in patients with unstable angina: association with systemic inflammation Eur Heart J 2004;25:1003-1008.[Abstract/Free Full Text]
- Sandri M, Adams V, Gielen S, et al. Effects of exercise and ischemia on mobilization and functional activation of blood-derived progenitor cells in patients with ischemic syndromes: results of 3 randomized studies Circulation 2005;111:3391-3399.[Abstract/Free Full Text]
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