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(Arteriosclerosis, Thrombosis, and Vascular Biology. 2008;28:968.)
© 2008 American Heart Association, Inc.

Clinical and Population Studies

Telomere Gap Between Granulocytes and Lymphocytes Is a Determinant for Hematopoetic Progenitor Cell Impairment in Patients With Previous Myocardial Infarction

Ioakim Spyridopoulos; Young Erben; Tim H. Brummendorf; Judith Haendeler; Klaus Dietz; Florian Seeger; Christine K. Kissel; Hans Martin; Jedrzej Hoffmann; Birgit Assmus; Andreas M. Zeiher; Stefanie Dimmeler

From the Departments of Cardiology and Molecular Cardiology (I.S., Y.E., J.H., F.S., C.K., J.H., B.A., A.M.Z., S.D.), Johann Wolfgang Goethe University of Frankfurt, Germany; the Department of Oncology and Hematology (T.H.B.), University Medical Center Hamburg-Eppendorf, Hamburg, Germany; the Department of Medical Biometry (K.D.), University of Tübingen, Germany; and the Department of Hematology (H.M.), Johann Wolfgang Goethe University of Frankfurt, Germany.

Correspondence to Ioakim Spyridopoulos, MD, Assistant Professor of Cardiology, Department of Cardiology and Molecular Cardiology, Johann Wolfgang Goethe University of Frankfurt, Theodor-Stern-Kai 7, 60590 Frankfurt am Main, Germany. E-mail spyridopoulos{at}em.uni-frankfurt.de

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.

Methods and 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).

Conclusion— 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.

In patients with CAD, telomere shortening is already present in mononuclear bone marrow cells. Telomere length depends on both age and the extent of CAD and correlates with bone marrow cell functionality. The telomere length difference between granulocytes and lymphocytes is the most sensitive determinant for telomere-associated bone marrow impairment.

Key Words: aging • coronary artery disease • telomeres • progenitor cells • lymphocytes

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Expanding the Concept of Telomere Dysfunction in Cardiovascular Disease

Pim van der Harst, Dirk J. van Veldhuisen, and Nilesh J. Samani
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