Response to Letter Regarding Article, “Circulating Endothelial Progenitor Cells in Patients With Eisenmenger Syndrome and Idiopathic Pulmonary Arterial Hypertension”
We thank Dr Asosingh et al for their interest in our study.1 Apparent disparity with their data2 probably reflects, at least in part, differences in defining endothelial progenitor cells (EPCs) and the number of patients studied with idiopathic pulmonary arterial hypertension. Asosingh et al2 measured only CD34+/CD133+ circulating cells, despite concern about the utility of CD133 as an EPC marker.3 Instead, we focused on CD34+/KDR+ cells, with or without CD133+ coexpression. Indeed, we agree that CD34+/CD133+ cell numbers are not reduced in idiopathic pulmonary arterial hypertension patients and the capacity of mononuclear cells to form colonies and incorporate in endothelial tubes is higher than healthy controls. Nonetheless, circulating CD34+/KDR+ EPCs were reduced in patients with idiopathic pulmonary arterial hypertension or Eisenmenger syndrome, and a dose-dependent relationship with sildenafil treatment was found,1 suggesting that therapeutic regimens influence these studies.
The possibility that mononuclear cell isolation steps affected the results was excluded by comparisons in healthy subjects and patients. Correcting EPC numbers, expressed as percentage of lymphomonocytic cells for actual cell counts in blood did not affect the results. Cell enumeration was consistent with previous FACS studies and acquisition of 100 000 events enabled sufficient EPCs to be identified for robust statistical analysis. Indeed, several studies have acquired fewer events in the lymphomonocytic cell gate.4 Finally, we did not classify CD34+/CD133+ cells by CD45 labeling but measured CD45low/CD34+ EPCs separately.
Diller GP, van Eijl S, Okonko DO, Howard LS, Ali O, Thum T, Wort SJ, Bedard E, Gibbs JS, Bauersachs J, Hobbs AJ, Wilkins MR, Gatzoulis MA, Wharton J. Circulating endothelial progenitor cells in patients with Eisenmenger syndrome and idiopathic pulmonary arterial hypertension. Circulation. 2008; 117: 3020–3030.
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