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Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure.

Abstract：

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.

journal_name

J Am Coll Cardiol

journal_title

Journal of the American College of Cardiology

authors

Kissel CK,Lehmann R,Assmus B,Aicher A,Honold J,Fischer-Rasokat U,Heeschen C,Spyridopoulos I,Dimmeler S,Zeiher AM

doi

10.1016/j.jacc.2007.01.095

subject

Has Abstract

pub_date

2007-06-19 00:00:00

pages

2341-9

issue

eissn

0735-1097

issn

1558-3597

pii

S0735-1097(07)01139-4

journal_volume

pub_type

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Selective functional exhaustion of hematopoietic progenitor cells in the bone marrow of patients with postinfarction heart failure.