Objective: Both obesity and the metabolic syndrome (MetS) have been independently linked with increased oxidative and inflammatory stress. This study tested the hypothesis that obesity with MetS is associated with greater oxidative and inflammatory burden compared with obesity alone. Research Methods and Procedures: Forty‐eight normal‐weight and 40 obese (20 without MetS; 20 with MetS) adults were studied. MetS was defined according to National Cholesterol Education Program Adult Treatment Panel III criteria. Plasma concentrations of oxidized low‐density lipoprotein, C‐reactive protein, tumor necrosis factor‐α, interleukin (IL)‐6, and IL‐18 were determined by enzyme immunoassay. Results: Plasma biomarkers of oxidative stress and inflammation were lowest in normal‐weight controls. Of note, obese MetS adults demonstrated significantly higher plasma concentrations of oxidized low‐density lipoprotein (62.3 ± 3.2 vs. 54.0 ± 4.0 U/L; p < 0.05), C‐reactive protein (3.0 ± 0.6 vs. 1.5 ± 0.3 mg/L; p < 0.01), tumor necrosis factor‐α (2.1 ± 0.1 vs. 1.6 ± 0.1 pg/mL; p < 0.05), IL‐6 (2.8 ± 0.4 vs. 1.4 ± 0.2 pg/mL; p < 0.01), and IL‐18 (253 ± 16 vs. 199 ± 16 pg/mL; p < 0.01), compared with obese adults without MetS. Discussion: These results suggest that MetS heightens oxidative stress and inflammatory burden in obese adults. Increased oxidative and inflammatory stress may contribute to the greater risk of coronary heart disease and cerebrovascular disease in obese adults with MetS.

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.

We determined the site-specific relations of hormone replacement therapy (HRT) and habitual exercise status with intima-media thickness (IMT) in both elastic (carotid) and muscular (femoral) arteries in 77 healthy postmenopausal women: 43 women were sedentary (20 no-HRT and 23 HRT users) and 34 women were endurance trained (14 no-HRT and 20 HRT users). Femoral IMT was not different among the sedentary HRT and endurance-trained no-HRT and HRT groups, but was lower (P < 0.005) in these three groups than in the sedentary no-HRT women. There were no significant group differences in carotid IMT. However, in older women (> or =65 yrs) carotid IMT was smaller (P < 0.05) in HRT compared with no-HRT women. We conclude that both endurance training and HRT status are independently associated with a smaller IMT and these effects are evident primarily in muscular arteries. These results suggest that HRT and habitual exercise may protect postmenopausal women against cardiovascular disease through influences on IMT. The site-specific relations may be due to a greater number of smooth muscle cells and plasticity of muscular arteries compared with elastic arteries and/or differences in heterogeneous influences such as metabolic requirements and hydrostatic pressures.

. Endothelial t-PA release is impaired in overweight and obese adults but can be improved with regular aerobic exercise. Am J Physiol Endocrinol Metab 289: E807-E813, 2005. First published June 28, 2005; doi:10.1152/ajpendo.00072.2005.-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 Ͻ25 kg/m 2 ); 22 overweight (BMI Ն25 and Ͻ30 kg/m 2 ); and 16 obese (BMI Ն30 kg/m 2 ). 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 ϳ45% lower (P Ͻ 0.01) in overweight (from 0.1 Ϯ 0.4 to 41.7 Ϯ 4.9 ng ⅐ 100 ml tissue Ϫ1 ⅐ min Ϫ1 ) and obese (Ϫ0.1 Ϯ 0.6 to 47.7 Ϯ 5.2 ng ⅐ 100 ml tissue Ϫ1 ⅐ min Ϫ1 ) compared with normal-weight (0.1 Ϯ 0.8 to 77.5 Ϯ 6.7 ng ⅐ 100 ml tissue Ϫ1 ⅐ min Ϫ1 ) 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 Ϫ0.3 Ϯ 0.5 to 37.1 Ϯ 4.9 ng ⅐ 100 ml tissue Ϫ1 ⅐ min Ϫ1 before training vs. 1.0 Ϯ 0.9 to 65.4 Ϯ 6.3 ng ⅐ 100 ml tissue Ϫ1 ⅐ min Ϫ1 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.endothelium; fibrinolysis; tissue-type plasminogen activator RECENT ESTIMATES INDICATE that over 60% of the adult population in the United States is either overweight or obese (21). Moreover, the incidence of overweight and obesity is highest in middle-aged and older adults and is thought to contribute to the increased risk of coronary artery disease, cerebrovascular disease, and atherothrombotic events in this segment of the population (37,39,40).It is now well accepted that endothelial dysfunction plays an important role in the initiation and progression of atherosclerosis (5, 45). A potential mechanism underlying the heightened atherothrombotic risk with obesity is impaired endothelial control of fibrinolysis. Endothelial cells are the principal site of synthesis and release of tissue-type plasminogen activator (t-PA), the key enzyme in initiating an endogenous fibrinolytic response, due to its ability to preferentially activate plasminogen on the surface of developing thrombi (15). Experimental...