Impaired endogenous fibrinolytic capacity in prehypertensive men.

Prehypertension (blood pressure (BP) 120-139/80-89 mm Hg) is associated with an increased risk for future atherothrombotic events. Although the mechanisms underlying this elevated risk are not completely understood, one possibility is that prehypertension is associated with impaired endothelial fibrinolytic capacity. We tested the hypothesis that vascular endothelial release of tissue-type plasminogen activator (t-PA) is impaired in prehypertensive men. Net endothelial release of t-PA was determined, in vivo, in response to intrabrachial infusions of bradykinin (12.5, 25, 50 ng per 100 ml tissue per min) and sodium nitroprusside at (1.0, 2.0, 4.0 µg per 100 ml tissue per min) in 42 middle-age and older men: 16 normotensive (BP range: 100-119/57-79 mm Hg); 16 prehypertensive (BP range: 120-139/76-89 mm Hg); and 10 hypertensive (BP range: 140-150/74-100 mm Hg). Net release of t-PA antigen was ~25% lower (P<0.05) in the prehypertensive (-0.9 ± 0.8 to 42.4 ± 5.3 ng per 100 ml tissue per min) compared with the normotensive (0.5 ± 1.0 to 53.9 ± 6.5 ng per 100 ml tissue per min) men. There was no significant difference in t-PA release between the hypertensive (-1.8 ± 1.6 to 40.8 ± 6.6 ng per 100 ml tissue per min) and prehypertensive groups. Sodium nitroprusside did not significantly alter the t-PA release in any group. These data indicate that endothelial t-PA release is diminished in prehypertensive men. Further, the level of impairment in t-PA release seen with clinical hypertension is already apparent in the prehypertensive state. Impaired endothelial fibrinolytic function may underlie the increased atherothrombotic risk associated with BP in the prehypertensive range.

Prehypertension and endothelial progenitor cell function.

Prehypertension is associated with significant damage to the coronary vasculature and increased rates of adverse cardiovascular events. Circulating endothelial progenitor cells (EPCs) are critical to vascular repair and the formation of new blood vessels. We tested the hypothesis that prehypertension is associated with EPC dysfunction. Peripheral blood samples were collected from 83 middle-aged and older adults (51 male and 32 female): 40 normotensive subjects (age 53±2 years; BP 111/74±1/1 mm Hg) and 43 prehypertensive subjects (age 54±2 years; 128/77±1/1 mm Hg). EPCs were isolated from peripheral blood, and EPC colony-forming capacity (colony-forming unit (CFU) assay), migratory activity (Boyden chamber) and apoptotic susceptibility (active caspase-3 concentrations) were determined. There were no significant differences in the number of EPC CFUs (10±2 vs 9±1), EPC migration (1165±82 vs 1120±84 fluorescent units) or active intracellular caspase-3 concentrations (2.7±0.3 vs 2.3±0.2 ng ml⁻¹) between the normotensive and prehypertensive groups. When groups were stratified into low prehypertension (n=27; systolic blood pressure: 120-129 mm Hg) and high prehypertension (n=16; 130-139 mm Hg), it was found that EPCs from the high prehypertensive group produced fewer (∼65%, P<0.05) CFUs compared with the low prehypertensive (4±1 vs 12±2) and normotensive adults. In conclusion, EPC colony-forming capacity is impaired only in prehypertensive adults with systolic BP greater than 130 mm Hg. Prehypertension is not associated with migratory dysfunction or enhanced apoptosis of EPCs.

Endothelial progenitor cell number and colony-forming capacity in overweight and obese adults.

OBJECTIVE: To investigate whether adiposity influences endothelial progenitor cell (EPC) number and colony-forming capacity. DESIGN: Cross-sectional study of normal weight, overweight and obese adult humans. PARTICIPANTS: Sixty-seven sedentary adults (aged 45-65 years): 25 normal weight (body mass index (BMI) or=30 kg/m(2); 18 males/6 females). All participants were non-smokers and free of overt cardiometabolic disease. MEASUREMENTS: Peripheral blood samples were collected and circulating EPC number was assessed by flow cytometry. Putative EPCs were defined as CD45(-)/CD34(+)/VEGFR-2(+)/CD133(+) or CD45(-)/CD34(+) cells. EPC colony-forming capacity was measured in vitro using a colony-forming unit (CFU) assay. RESULTS: Number of circulating putative EPCs (either CD45(-)/CD34(+)/VEGFR-2(+)/CD133(+) or CD45(-)/CD34(+) cells) was lower (P<0.05) in obese (0.0007+/-0.0001%; 0.050+/-0.006%) compared with overweight (0.0016+/-0.0004%; 0.089+/-0.019%) and normal weight (0.0015+/-0.0003%; 0.082+/-0.008%) adults. There were no differences in EPC number between the overweight and normal weight groups. EPC colony formation was significantly less in the obese (6+/-1) and overweight (4+/-1) compared with normal weight (9+/-2) adults. CONCLUSION: These results indicate that: (1) the number of circulating EPCs is lower in obese compared with overweight and normal weight adults; and (2) EPC colony-forming capacity is blunted in overweight and obese adults compared with normal weight adults. Impairments in EPC number and function may contribute to adiposity-related cardiovascular risk.