Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure.
OBJECTIVE
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.
Kissel
Christine K
CK
Department of Cardiology, Johann Wolfgang Goethe-University Frankfurt, Frankfurt, Germany.
Lehmann
Ralf
R
Assmus
Birgit
B
Aicher
Alexandra
A
Honold
Jörg
J
Fischer-Rasokat
Ulrich
U
Heeschen
Christopher
C
Spyridopoulos
Ioakim
I
Dimmeler
Stefanie
S
Zeiher
Andreas M
AM
D000293:Adolescent; D000328:Adult; D000368:Aged; D000369:Aged, 80 and over; D001853:Bone Marrow; D001854:Bone Marrow Cells / Q000378:metabolism*; D002311:Cardiomyopathy, Dilated / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology*; D002465:Cell Movement / Q000502:physiology; D003114:Colony-Forming Units Assay; D015897:Comorbidity; D005260:Female; D005434:Flow Cytometry; D006342:Heart Rupture, Post-Infarction; D006412:Hematopoietic Stem Cells / Q000378:metabolism*; D006801:Humans; D008297:Male; D020780:Matrix Metalloproteinase 9 / Q000097:blood; D008875:Middle Aged; D009203:Myocardial Infarction / Q000150:complications; D017202:Myocardial Ischemia / Q000097:blood* / Q000453:epidemiology / Q000503:physiopathology*; D012907:Smoking / Q000453:epidemiology
D020780:Matrix Metalloproteinase 9