Author + information
- Received February 14, 2006
- Revision received January 11, 2007
- Accepted January 22, 2007
- Published online June 19, 2007.
- Christine K. Kissel, MD1,
- Ralf Lehmann, MD,
- Birgit Assmus, MD,
- Alexandra Aicher, MD,
- Jörg Honold, MD,
- Ulrich Fischer-Rasokat, MD,
- Christopher Heeschen, MD,
- Ioakim Spyridopoulos, MD,
- Stefanie Dimmeler, PhD and
- Andreas M. Zeiher, MD⁎ ()
- ↵⁎Reprint requests and correspondence:
Dr. Andreas M. Zeiher, Department of Cardiology, University of Frankfurt, Theodor Stern-Kai 7, 60590 Frankfurt, Germany.
Objectives This study investigated whether reduced levels of circulating endothelial progenitors cells (EPCs) in chronic heart failure (CHF) are secondary to an exhaustion of hematopoietic stem cells (HSCs) in the bone marrow or to reduced mobilization.
Background Circulating EPCs presumably originate from bone marrow-derived HSC. Persistent mobilization of EPCs was shown to be associated with favorable left ventricular infarct remodeling processes.
Methods We assessed the number and functional capacity of EPCs in 17 healthy controls, 25 patients with ischemic cardiomyopathy (ICM), and 20 patients with dilated cardiomyopathy (DCM). To document an impairment of HSC function in the bone marrow, the colony-forming unit capacity of bone marrow–derived mononuclear cells and the number of CD34+HSCs were examined in 6 healthy volunteers, 94 ICM patients, and 25 DCM patients.
Results The number of EPCs was reduced in CHF, irrespective of its etiology. In contrast, the migratory capacity was selectively impaired in EPCs of ICM patients (4.8 ± 4.0 migrated cells; DCM 9.7 ± 5.8; p = 0.02). On multivariate analysis, ICM, advanced New York Heart Association functional class, and CHF were independent predictors of functional EPC impairment. The number of bone marrow-derived CD34+cells did not differ between the CHF populations. However, colony-forming units (CFUs) were selectively reduced in ICM patients (54.4 ± 24.6; DCM 68.1 ± 26.9; p < 0.02). Ischemic cardiomyopathy was the only independent predictor of impaired CFU capacity. Impaired CFU capacity was associated with reduced matrix metalloproteinase-9 activity in the bone marrow plasma.
Conclusions Ischemic cardiomyopathy is associated with selective impairment of progenitor cell function in the bone marrow and in the peripheral blood, which may contribute to an unfavorable left ventricular (LV) remodeling process.
↵1 Dr. Kissel was supported in part by the Dr. August Scheidel Foundation and the Deutsche Forschungsgemeinschaft (DFG Wa 1461/2-2).
The authors of this article belong to the European Vascular Genomics Network, a Network of Excellence supported by the European Community’s Sixth Framework Programme for Research Priority 1: “Life sciences, genomics and biotechnology for health” (Contract No. LSHM-CT-2003-503254). The first two authors contributed equally to this work.
- Received February 14, 2006.
- Revision received January 11, 2007.
- Accepted January 22, 2007.
- American College of Cardiology Foundation