Telomere gap between granulocytes and lymphocytes is a determinant for hematopoetic progenitor cell impairment in patients with previous myocardial infarction.
OBJECTIVE
We have previously demonstrated that 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 remodeling process.


RESULTS
With this study, we intended to identify the influence of telomere length on bone marrow functionality in 50 patients with coronary artery disease (CAD) and previous myocardial infarction. Mean telomere length (mTL) was measured simultaneously in peripheral blood leukocytes and mononuclear bone marrow cells (BMC), using the flow-FISH method. Telomere erosion already occurred at the bone marrow level, whereby age (39 bp/yr, P=0.025) and the number of affected vessels (434 bp/vessel, P=0.029) were the only independent predictors. Lymphocytes demonstrated significant TL shortening between BMCs and peripheral blood in CAD patients (-1011+/-897 bp) as opposed to an increase in a young control group (+235+/-459 bp, P<0.001). SDF- and VEGF-specific migration of BMCs correlated with mTL of lymphocytes (r=0.42, P<0.001) and was significantly reduced in CAD patients. Finally, the telomere length difference between granulocytes and lymphocytes was the most determinant for telomere-associated bone marrow impairment (P<0.001).


CONCLUSIONS
In patients with CAD, telomere shortening of BMCs is dependent on both age and the extent of CAD and correlates with bone marrow cell functionality.
Spyridopoulos
Ioakim
I
Department of Cardiology, Wolfgang Goethe University of Frankfurt, Germany. spyridopoulos@em.uni-frankfurt.de
Erben
Young
Y
Brummendorf
Tim H
TH
Haendeler
Judith
J
Dietz
Klaus
K
Seeger
Florian
F
Kissel
Christine K
CK
Martin
Hans
H
Hoffmann
Jedrzej
J
Assmus
Birgit
B
Zeiher
Andreas M
AM
Dimmeler
Stefanie
S
D000328:Adult; D000368:Aged; D050197:Atherosclerosis / Q000473:pathology / Q000503:physiopathology; D015415:Biomarkers / Q000097:blood; D001853:Bone Marrow / Q000473:pathology / Q000503:physiopathology; D016022:Case-Control Studies; D003324:Coronary Artery Disease / Q000473:pathology / Q000503:physiopathology; D005260:Female; D006098:Granulocytes / Q000473:pathology* / Q000502:physiology; D006412:Hematopoietic Stem Cells / Q000473:pathology* / Q000502:physiology; D006801:Humans; D008214:Lymphocytes / Q000473:pathology* / Q000502:physiology; D008297:Male; D008875:Middle Aged; D009203:Myocardial Infarction / Q000097:blood / Q000473:pathology* / Q000503:physiopathology; D011237:Predictive Value of Tests; D012044:Regression Analysis; D016615:Telomere / Q000473:pathology* / Q000502:physiology
D015415:Biomarkers