NUMBER AND REPLATING CAPACITY OF ENDOTHELIAL COLONY FORMING CELLS ARE TELOMERE LENGTH DEPENDENT: IMPLICATION FOR HUMAN ATHEROGENESIS

Abstract

Abstract Objective: Short leukocyte telomere length (TL) is associated with atherosclerotic cardiovascular disease. Endothelial repair plays a key role in the development of atherosclerosis. To explore a potential role of short TL in atherogenesis, we examined associations between TL and proliferative dynamics of endothelial colony forming cells (ECFCs), which behave as progenitor cells displaying endothelial repair activity. Design and method: To isolate ECFCs, we performed a clonogenic assay on blood samples from 116 participants (24 to 94 years old) in the TELARTA (Telomere in Arterial Aging) study. We detected no ECFC clone in 29 (Group 1), clones with no replating capacity in other 29 (Group 2), and clones with replating capacity in additional 58 (Group 3). TL was measured by Southern blotting in leukocytes (LTL) and ECFCs (ECFC-TL). Results: Age- and sex-adjusted LTL (mean ± SEM) was the shortest in Group 1 (6.51 ± 0.13 kb), longer in Group 2 (6.69 ± 0.13 kb) and the longest in Group 3 (6.78 ± 0.09 kb) (p < 0.05). In group 3, ECFC-TL was associated with the number of detected clones (p < 0.01). ECFC-TL (7.98 ± 0.13 kb) was longer than LTL (6.74 ± 0.012 kb) (p < 0.0001) and both parameters were strongly correlated (r = 0.82; p < 0.0001). Conclusions: Individuals with longer telomeres display a higher number of self-renewing ECFCs suggesting that they might have a better endothelial repair capacity. Our results also indicate that LTL, as a proxy of TL dynamics in ECFCs, could be used as a surrogate marker of endothelial repair capacity in clinical and laboratory practice due to easy accessibility of leukocytes.