Abstract 5161: Accelerated Telomere Shortening in CD8+ T-lymphocytes From Patients With Coronary Heart Disease Links Cytomegalovirus-Induced T Cell Response and Deterioration of Myocardial Function

Abstract

Shortening of mean telomere length (TL) in white blood cells is correlated with the development of coronary heart disease (CHD) as well as with increased mortality due to infectious disease. The goal of this study was to investigate whether TL 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 and progenitor cells (PBPC) obtained from the same patients. TL was measured by Multicolor Flow-FISH in 12 leukocyte subpopulations following immunomagnetic bead sorting. We investigated TL in 14 young (mean age 25 years) and 13 old healthy male volunteers (65 years), as well as in 25 age-matched patients (65 years) suffering from CHD. We show that TL in granulocytes and monocytes mirrors TL of CD34+ PBPC extremely well (r=0.95; p<0.0001), in patients as well as in healthy adults. TL was approximately 500 base pairs shorter in leukocytes from patients with CHD compared to their age-matched controls. This difference was identical for CD34+ PBPC, monocytes, granulocytes, B-lymphocytes and CD4+ T-cells. Surprisingly, only in cytotoxic CD8+ T lymphocytes (CTL), we found a substantially increased TL deficit of 1000 bp (p<0.001 vs. CD4+ cells) in CHD patients as opposed to controls. Further analysis revealed that TL shortening was particularly pronounced in CD8+CD28− T-cells obtained from cytomegalovirus (CMV) seropositive CHD patients, whereas such a difference was not observed in healthy CMV positive as opposed to CMV negative controls. Moreover, TL shortening of CD8+CD45RA+ T-cells from CMV seropositive patients correlated with the decrease of left ventricular function in CHD patients (r=0.635, p=0.001). In contrast, CMV seropositivity did not have any influence on TL in myeloid cells or PBPC. Conclusion: Our data suggest that TL shortening in CHD is inherited, thus affecting the baseline TL of all peripheral blood cell populations including PBPC. In addition, CMV seropositive patients exhibit further shortening of their CTLs. Surprisingly, telomere length shortening of CTLs in CMV seropositive individuals demonstrated a very strong correlation with cardiac dysfunction, suggesting a mechanistic link between CHD and immunosenescence.