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Objective: We hypothesized that the capacity of the endothelium to release tissue-type plasminogen activator is blunted in postmenopausal women with long (TA)(n) repeat alleles (> or = 18 repeats)., Study Design: Forty-two healthy postmenopausal women were studied: 10 women with short allele genotypes (both alleles, <18 repeats; age, 59 +/- 2 years), 8 women with long allele genotypes (both alleles, > or = 18 repeats; age, 59 +/- 3 years), and 24 women with mixed allele genotypes (1 short and 1 long allele; age, 56 +/- 1 years). Net endothelial tissue-type plasminogen activator release was determined in response to intra-arterial bradykinin and sodium nitroprusside., Results: Tissue-type plasminogen activator release in response to bradykinin was highest in homozygotes for the short allele. The total amount of tissue-type plasminogen activator antigen that was released was significantly higher (>55%) in the short (452 +/- 68 ng/100 mL tissue) compared with the mixed (248 +/- 27 ng/100 mL tissue) and long allele (290 +/- 53 ng/100 mL tissue) groups., Conclusion: Our results demonstrate that the long (TA)n dinucleotide repeat allele is associated with blunted endothelial tissue-type plasminogen activator release in healthy postmenopausal women.

The capacity of vascular endothelium to locally release tissue-type plasminogen activator (t-PA) represents an important endogenous defence mechanism against intravascular fibrin deposition and thrombosis. We determined the influence of chronic and acute oestrogen administration on endothelial t-PA release in postmenopausal women. Sixty-three healthy postmenopausal women were studied: 31 non-users (age 58 +/- 1 years) and 32 users of hormone replacement therapy, including oestrogen alone (ORT: 62 +/- 2 years; n = 15) and in combination with progesterone (HRT: 57 +/- 1 years; n = 17). Net endothelial t-PA release was determined in vivo, in response to intrabrachial infusions of bradykinin and sodium nitroprusside. To examine the acute effects of oestrogen on endothelial t-PA release, bradykinin and sodium nitroprusside dose-response curves were repeated in the presence of 17 beta-oestradiol in 20 of the 31 non-users. Net endothelial release of t-PA was ~30 % higher (P < 0.01) in women taking ORT (from 2.0 +/- 1.0 to 83.6 +/- 9.2 ng (100 ml tissue)-1 min-1) compared with those taking HRT (from 1.4 +/- 0.4 to 63.5 +/- 5.6 ng (100 ml tissue)-1 min-1) and those not taking supplementation (1.0 +/- 0.7 to 63.0 +/- 4.7 ng (100 ml tissue)-1 min-1). Intra-arterial infusion of 17 beta-oestradiol significantly potentiated bradykinin-induced t-PA release. Net endothelial release of t-PA was approximately 45 % higher (P < 0.01) after (from 1.0 +/- 0.8 to 87.4 +/- 9.9 ng (100 ml tissue)-1 min-1) versus before (1.2 +/- 0.6 to 60.8 +/- 5.6 ng (100 ml tissue)-1 min-1) acute 17 beta-oestradiol administration. Our results suggest that oestrogen has a direct modulatory effect on the capacity of the endothelium to release t-PA in healthy postmenopausal women. However, progesterone appears to oppose the favourable influence of oestrogen on endothelial fibrinolytic capacity.

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]

Objective: We hypothesized that the capacity of the endothelium to release tissue-type plasminogen activator is blunted in postmenopausal women with long (TA) n repeat alleles (⩾ 18 repeats). Study design: Forty-two healthy postmenopausal women were studied: 10 women with short allele genotypes (both alleles, < 18 repeats; age, 59 ± 2 years), 8 women with long allele genotypes (both alleles, ⩾18 repeats; age, 59 ± 3 years), and 24 women with mixed allele genotypes (1 short and 1 long allele; age, 56 ± 1 years). Net endothelial tissue-type plasminogen activator release was determined in response to intra-arterial bradykinin and sodium nitroprusside. Results: Tissue-type plasminogen activator release in response to bradykinin was highest in homozygotes for the short allele. The total amount of tissue-type plasminogen activator antigen that was released was significantly higher (>55%) in the short (452 ± 68 ng/100 mL tissue) compared with the mixed (248 ± 27 ng/100 mL tissue) and long allele (290 ± 53 ng/100 mL tissue) groups. Conclusion: Our results demonstrate that the long (TA)n dinucleotide repeat allele is associated with blunted endothelial tissue-type plasminogen activator release in healthy postmenopausal women. [ABSTRACT FROM AUTHOR]