Aging Is Associated with a Proapoptotic Endothelial Progenitor Cell Phenotype

Abstract

The aim of this study was to determine if aging is associated with enhanced endothelial progenitor cell (EPC) sensitivity to apoptosis. Cells with phenotypic EPC characteristics were isolated from healthy, nonobese young (age 25 ± 1 years) and older (61 ± 1 years) men. Intracellular active caspase-3 concentrations in response to staurosporine stimulation were approximately 35% higher (p < 0.05) in EPCs from older (3.15 ± 0.29 pg/ml) compared with young (2.33 ± 0.24 pg/ml) men. Protein expression of Akt, p70 S6-kinase and Bcl-2 was markedly lower (approx. 35, 75 and 60%, respectively, all p < 0.05) in EPCs from older compared with young men, whereas there were no age-related differences in either 14-3-3Ε or Bax expression. Additionally, EPC telomerase activity was 57% lower (p < 0.05) in older (0.18 ± 0.11 AU) versus young (0.43 ± 0.11 AU) men. These results indicate that aging is associated with a proapoptotic EPC phenotype characterized by decreased expression of key antiapoptotic proteins associated with the PI-3-kinase signaling pathway and reduced telomerase activity. These age-related changes likely contribute, in part, to the diminished ability of EPCs to resist an apoptotic stimulus in older men. Increased susceptibility to apoptosis may contribute to the numerical and functional impairments observed in EPCs with aging.

Evaluation of cardiac muscle microvessel density in children diagnosed with cyanotic heart defects

“…Kushner et al [25] previously demonstrated that changes in subpopulations of CD31-positive cells decrease angiogenic potential and augment the probability of developing age-related circulatory diseases. Thus, MVD has been recognized as a prognostic factor for the adaptive tissue potential for anoxia [26].…”

Circulating endothelial and progenitor cells: Evidence from acute and long-term exercise effects

“…It has been also documented that EPCs are significantly reduced in elderly populations [20] , and appear to have elevated apoptotic susceptibility [21] . The number and function of early EPCs isolated from the peripheral blood of 20 healthy young and 20 old (61 ± 2 years) individuals have been investigated by Heiss et al [22] .…”

Expresión disminuida de caspasa 3 asociada al polimorfismo del gen del antígeno-4 asociado a linfocito T-citotóxico (CTLA4) en pacientes chilenos con diabetes tipo 1

“…Sin embargo, esta diferencia de edad podría estar afectando la actividad de caspasa 3. En otros modelos celulares (cardiomiocitos en cultivo, células progenitoras endoteliales y músculo) se ha observado que la concentración de caspasa 3 está aumentada y que su actividad tiende a ser mayor con la edad [37][38][39] . Este antecedente es relevante y a pesar de que no hay antecedentes en CMPs y que los controles también son jóvenes, debiera interpretarse con cautela.…”