Abstract 3354: Increase of Telomere Gap between Granulocytes and Lymphocytes in Patients with Previous Myocardial Infarction: A Novel Measure for Accelerated Telomere Erosion

Abstract

Individuals with age-corrected reduction of total leukocyte telomere length have been shown to exhibit a remarkable increase in mortality from cardiovascular and infectious complications. Given the considerable interindividual variability of telomere length in healthy adults due to genetic differences already present at birth and the heterogeneity in composition of the total leukocyte compartment, extensive study populations are required to detect accelerated telomere shortening between age-matched groups. With this study, we intended to identify a parameter to improve prediction of individual telomere erosion in patients (pts) with coronary artery disease and previous myocardial infarction (CAD). Methods: Mean telomere length (mTL) was measured in 63 CAD pts (mean age 65±4 years, mean ejection fraction 31±9%) and 23 age-matched healthy controls (65±4 years). Using the flow-FISH method, we were able to distinguish between myeloid and lymphoid cell populations in peripheral blood cells as well as in bone marrow mononuclear cells (BMC). Results: The difference between mTL of the granulocyte and lymphocyte population (ΔTEL Gr-Ly ) was significantly increased from 742 ± 396 base pairs (bp) in the control group to 1055±570 bp in CAD pts (p=0.018). Age was the only independent predictor for telomere length of BMCs. Lymphocytes, but not granulocytes, demonstrated significant telomere shortening between BMCs and peripheral blood in CAD patients (−444 ± 624 bp) as opposed to an increase in a young and healthy control group (+307 ± 372 bp) (p<0.001). Using immunomagnetic cell sorting, telomerase activity (TA) was determined in freshly isolated white blood cell subpopulations. Surprisingly, TA could not be detected in peripheral blood granulocytes (CD15 + granulocytes) from CAD pts. In contrast, CD4 + T-lymphocytes contained the highest amount of TA, compared to CD8 + cells and B-lymphocytes. Conclusions: Our results suggest that primarily peripheral blood lymphocytes - and not granulocytes - can develop stress-induced telomere erosion in CAD. Therefore the base pair length difference between the two populations provides a valuable parameter to detect telomere erosion in patients with CAD, largely independent of the hereditary influence on mTL.