| Accelerated telomere shortening in leukocyte subpopulations of patients with coronary heart disease: role of cytomegalovirus seropositivity. | |
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MedLine Citation:
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PMID: 19770396 Owner: NLM Status: MEDLINE |
Abstract/OtherAbstract:
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BACKGROUND: Shortening of mean telomere length (TL) in white blood cells is correlated with the development of coronary heart disease (CHD) and with increased mortality due to infectious disease. The goal of the present study was to investigate whether telomere shortening in CHD is restricted to specific peripheral blood lymphocyte and/or myeloid cell subpopulations. Results were correlated to TL in CD34+ hematopoietic peripheral blood stem cells and progenitor cells obtained from the same individual patients. METHODS AND RESULTS: TL was measured by multicolor flow cytometry-fluorescent in situ hybridization in 12 leukocyte subpopulations after immunomagnetic bead sorting. We investigated TL in 14 young (mean age 25 years) and 13 older (mean age 65 years) healthy male volunteers and in 25 age-matched patients with CHD (mean age 65 years). We show that TL in granulocytes and monocytes mirrors TL of CD34+ peripheral blood stem cells and progenitor cells extremely well (r=0.95, P<0.0001) in patients and in healthy adults. TL was approximately 0.5 kilobases (kb) shorter in leukocytes from patients with CHD than in their age-matched control subjects. This difference was identical for CD34+ peripheral blood stem cells and progenitor cells, monocytes, granulocytes, B lymphocytes, and CD4+ T cells, including their memory and naïve subpopulations. Surprisingly, only in cytotoxic CD8+ T lymphocytes, we found a substantially increased TL deficit of 1.0 kb in CHD patients as opposed to control subjects. Further analysis revealed that TL shortening was particularly pronounced in CD8+CD28(-) T cells obtained from cytomegalovirus-seropositive CHD patients, whereas such a difference was not observed in healthy cytomegalovirus-positive as opposed to cytomegalovirus-negative control subjects. Finally, TL shortening of CD8+CD45(RA+) T cells was correlated with the decrease in left ventricular function in CHD patients (r=0.629, P=0.001). CONCLUSIONS: Telomere shortening in patients with CHD could potentially be attributed to either inherited TL shortening or acquired accelerated telomere shortening restricted to the hematopoietic system, which affects the baseline TL of all peripheral blood cell populations, including peripheral blood stem cells and progenitor cells. In addition, cytomegalovirus-seropositive patients but not healthy control subjects exhibited further shortening of their cytotoxic T lymphocytes. Surprisingly, TL shortening of CD8+ T lymphocytes in CHD patients demonstrated a very strong correlation with cardiac dysfunction, which suggests a mechanistic link between CHD and immunosenescence. |
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Authors:
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Ioakim Spyridopoulos; Jedrzej Hoffmann; Alexandra Aicher; Tim H Brümmendorf; Hans W Doerr; Andreas M Zeiher; Stefanie Dimmeler |
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Publication Detail:
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Type: Journal Article; Research Support, Non-U.S. Gov't Date: 2009-09-21 |
Journal Detail:
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Title: Circulation Volume: 120 ISSN: 1524-4539 ISO Abbreviation: Circulation Publication Date: 2009 Oct |
Date Detail:
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Created Date: 2009-10-06 Completed Date: 2009-10-23 Revised Date: - |
Medline Journal Info:
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Nlm Unique ID: 0147763 Medline TA: Circulation Country: United States |
Other Details:
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Languages: eng Pagination: 1364-72 Citation Subset: AIM; IM |
Affiliation:
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Institute of Human Genetics, Newcastle University, International Centre for Life, Central Parkway, Newcastle Upon Tyne NE13BZ, United Kingdom. ioakim.spyridopoulos@newcastle.ac.uk |
Export Citation:
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| MeSH Terms | |
Descriptor/Qualifier:
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Adult Aged CD8-Positive T-Lymphocytes / immunology Coronary Disease / genetics*, immunology, virology* Cytomegalovirus / genetics* Cytomegalovirus Infections / complications*, immunology Flow Cytometry Granulocytes / physiology Humans In Situ Hybridization, Fluorescence Inflammation / genetics, immunology, physiopathology Leukocytes / physiology* Male Middle Aged Monocytes / physiology Myocardial Infarction / physiopathology Reference Values Telomerase / metabolism Telomere / physiology*, ultrastructure Ventricular Dysfunction, Left / physiopathology |
| Chemical | |
Reg. No./Substance:
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EC 2.7.7.49/Telomerase |
From MEDLINE®/PubMed®, a database of the U.S. National Library of Medicine
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