Abstract 702: Acceleration Of Telomere Erosion In Specific Subpopulations Of Peripheral Blood Leukocytes In Patients With Ischemic Cardiomyopathy
Telomere shortening has been identified as a negative prognostic marker for the development of coronary artery disease and was related to the severity of heart failure. However, all studies so far exclusively measured the mean telomere length (TL) of total peripheral blood leukocytes. In order to determine whether telomere shortening is caused by a global reduction of telomere length in all cells or specifically occurs in individual subsets, we determined the telomere length in purified subpopulations.
Methods: We studied 6 male patients (pts) with ischemic cardiomyopathy (ICM) (age 66.2 ±3.59 y, EF 22%, NT-proBNP 10012±16032 pg/ml), 7 age-matched healthy controls (O: 66.4 ± 0.9 y, NT-proBNP 74 ± 46 pg/ml) and 14 young healthy controls (26 ± 1.5 y). Mean TL was measured in peripheral CD34+ progenitor cells, CD15+ granulocytes, CD14+ monocytes, CD19+ B cells and T cell subpopulations (CD4+ and CD8+) by multicolor Flow-FISH after immunomagnetic cell sorting. Purity (>95%) of sorted subpopulations was confirmed by surface marker staining.
Results: TL was significantly reduced in all subpopulations isolated from healthy old versus young individuals consistent with an age-related reduction in total TL in healthy controls. However, when comparing patients with ICM with aged-matched controls (ICM versus O), telomere length in CD8+ lymphocytes (4993 ± 804 bp vs. 6799 ± 1439 bp, p<0.01), and monocytes (6752 ± 496 bp vs. 7794 ± 909 bp, p<0.05) was significantly shorter in ICM pts. Moreover, telomere length of CD34+ stem cells was reduced by 790 bp in the ICM group (p=0.07). In contrast, CD4+ lymphocytes, granulocytes and B cells isolated from ICM pts showed no significant difference in TL compared to age-matched healthy controls.
Conclusions: Our results for the first time identify specific cell populations affected by age-independent telomere erosion in patients with ICM. The accelerated telomere erosion in ICM patients particularly in CD8+ lymphocytes may contribute to immunosenescence, while the reduction of telomere length in CD34+ stem cells may harbour important implications for cell-based therapies.