RESUMO
Numerical and functional impairment of circulating endothelial progenitor cells (EPCs) is thought to contribute to vascular aging and the associated increase in cardiovascular risk. We tested the following hypotheses: 1) EPC clonogenic and migratory capacity decrease progressively with age in healthy, sedentary adult men; and 2) regular aerobic exercise will improve EPC clonogenic and migratory capacity in previously sedentary middle-aged and older men. Peripheral blood samples were collected from 46 healthy sedentary men: 10 young (26 +/- 1 yr), 15 middle-aged (47 +/- 1 yr), and 21 older (63 +/- 1 yr). Mononuclear cells were isolated and preplated for 2 days, and nonadherent cells were further cultured for 7 days to determine EPC colony-forming units. Migratory activity of EPCs was determined using a modified Boyden chamber. Ten sedentary middle-aged and older men (59 +/- 3 yr) were studied before and after a 3-mo aerobic exercise intervention. The number of EPC colony-forming units was approximately 75% lower (P < 0.01) in middle-aged (12 +/- 3) and older (8 +/- 2) compared with young (40 +/- 7) men. There was no difference in colony count between middle-aged and older men. EPC migration (fluorescent units) was significantly reduced in older (453 +/- 72) compared with young (813 +/- 114) and middle-aged (760 +/- 114) men. The exercise intervention increased (P < 0.05) both EPC colony-forming units (10 +/- 3 to 22 +/- 5) and migratory activity (683 +/- 96 to 1,022 +/- 123) in previously sedentary middle-aged and older men. These results provide further evidence that aging adversely affects EPC function. Regular aerobic-endurance exercise, however, is an effective lifestyle intervention strategy for improving EPC clonogenic and migratory capacity in middle-aged and older healthy men.
Assuntos
Células-Tronco Adultas/fisiologia , Envelhecimento/fisiologia , Movimento Celular/fisiologia , Proliferação de Células , Exercício Físico/fisiologia , Adulto , Idoso , Ensaio de Unidades Formadoras de Colônias , Estudos Transversais , Humanos , Masculino , Pessoa de Meia-IdadeRESUMO
Endothelial nitric oxide synthase (eNOS) activity has been shown to play a pivotal role in the mobilization of endothelial progenitor cells (EPCs) into the circulation from bone marrow. Indeed, in eNOS-deficient mice, exercise-induced EPC mobilization is severely diminished. We determined ex vivo whether circulating EPC colony-forming capacity and migratory activity are influenced by eNOS activity. Peripheral-blood mononuclear cells were isolated from 20 healthy adults and preplated for 2 days, and nonadherent cells were further cultured for 7 days in the presence and absence of N-nitro-L-arginine methyl ester (L-NAME, 300 microM, an eNOS antagonist) to determine EPC colony-forming units. Migratory activity of EPCs, cultured with and without L-NAME (300 microM) was determined by utilizing a modified Boyden chamber. The number of EPC colony-forming units was not significantly different when cultured in the absence or presence of L-NAME (21+/-5 vs 18+/-5). Moreover, eNOS inhibition did not alter EPC migratory activity; mean fluorescence was similar in samples cultured with (983+/-126 RFUs) and without (962+/-105 RFUs) L-NAME. These in vitro results suggest that, in contrast to EPC mobilization from the bone marrow, eNOS does not exert a modulatory influence on the functional capacity of circulating EPCs to either form colonies or migrate.