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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 ± I 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 ~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. [ABSTRACT FROM AUTHOR]

Endothelial release of tissue-type plasminogen activator (t-PA) regulates fibrinolysis and is considered to be a primary endogenous defense mechanism against thrombosis. Adiposity is associated with an increased risk of atherothrombotic events. We determined the influence of overweight and obesity on the capacity of the vascular endothelium to release t-PA and the effects of regular aerobic exercise on endothelial t-PA release in previously sedentary overweight and obese adults. First, we studied 66 sedentary adults: 28 normal-weight (BMI «25 kg/m²); 22 overweight (BMI ≥25 and «30 kg/m²); and 16 obese (BMI ≥30 kg/m²). Net endothelial t-PA release was determined in vivo in response to intrabrachial infusions of bradykinin (BK) and sodium nitroprusside. Second, we studied 17 overweight and obese adults who completed a 3-mo aerobic exercise intervention. Net release of t-PA in response to BK was ∼45% lower (P « 0.01) in overweight (from 0.1 ± 0.4 to 41.7 ± 4.9 ng·100 ml tissue-1·min-1) and obese (-0.1 ± 0.6 to 47.7 ± 5.2 ng·100 ml tissue-1·min-1) compared with normal-weight (0.1 ± 0.8 to 77.5 ± 6.7 ng·100 ml tissue-1·min-1) adults. There was no difference in t-PA release between the overweight and obese groups. Exercise training significantly increased t-PA release capacity in overweight and obese adults (from -0.3 ± 0.5 to 37.1 ± 4.9 ng·100 ml tissue-1·min-1 before training vs. 1.0 ± 0.9 to 65.4 ± 6.3 ng·100 ml tissue-1·min-1 after training) to levels comparable with those of their normal-weight peers. These results indicate that overweight and obesity are associated with profound endothelial fibrinolytic dysfunction. Importantly, however, regular aerobic exercise can increase the capacity of the endothelium to release t-PA in this at-risk population. [ABSTRACT FROM AUTHOR]

Middle-aged women have a lower prevalence and incidence of cardiovascular events compared with men. The mechanisms responsible for this gender-specific difference are unclear. Numeric and functional impairments of bone marrow–derived circulating endothelial progenitor cells (EPCs) are associated with increased cardiovascular and cerebrovascular morbidity and mortality. It is currently unknown whether there are gender-related differences in EPC number and function in middle-aged adults. We tested the hypothesis that EPCs isolated from middle-aged women demonstrate greater colony-forming capacity and migratory activity compared with men of similar age. Peripheral blood samples were collected from 50 sedentary adults, 25 men (59 ± 1 years of age) and 25 women (58 ± 1 years of age). 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. The number of EPC colony-forming units was significantly higher (∼150%) in samples collected from women (16 ± 3) compared with that collected from men (7 ± 1). In addition, EPC migration (relative fluorescent units) was ∼40% greater in women (729 ± 74) than in men (530 ± 67). In conclusion, these results demonstrate that EPC colony-forming capacity and migratory activity are higher in middle-aged women than in men. [Copyright &y& Elsevier]