Abstract 388: Regular Aerobic Exercise Enhances Endothelium tPA Release in Adults With HIV-1

Abstract

HIV-1 infection is associated with vascular endothelial dysfunction and increased risk of cardiovascular disease. We have previously demonstrated that the capacity of the endothelium to release tissue-type plasminogen activator (t-PA), the primary activator of endogenous fibrinolysis, is markedly impaired in HIV-1-seropositive compared with seronegative adults, regardless of antiretroviral therapy. Endothelial fibrinolytic dysfunction underlies thrombogenesis and is thought to contribute to the increased risk of atherothrombotic events in HIV-1-infected adults. Regular aerobic exercise can beneficially affect vascular health and reduce cardiovascular risk. However, whether aerobic exercise training can alleviate HIV-1-related endothelial fibrinolytic dysfunction is unknown. In an ongoing study, we are testing the hypothesis that regular aerobic exercise improves endothelial t-PA release in HIV-1 seropositive adults. Net endothelial release of t-PA was determined, in vivo, in response to intrabrachial infusions of bradykinin (BK: 125-500 ng/min) and sodium nitroprusside (SNP: 2-8 μg/min) before and after a 3-month aerobic exercise intervention. To date, 10 HIV-1 seropositive adults (age: 38+2 yr; 8 M/2 F) have completed the exercise intervention (walking ~5.1 d/wk, ~50 min/d @ ~70% of maximal heart rate). There were no changes in body weight, % body fat, or maximal oxygen consumption after exercise training, however, treadmill exercise time to exhaustion increased 25% (from 9.0+0.4 to 11.2+0.4 min; p<0.01). The capacity of the endothelium to release t-PA in response to BK was significantly higher after (-0.58+1.5 to 102.3+15.5 ng/100 mL tissue/min) vs before (-0.8+1.0 to 48.7+10.1 ng/100 mL tissue/min) exercise training. In addition, total amount of t-PA released (area under the BK curve) was increased more than two-fold (329+73 vs 728+108 ng/100 mL tisuue) in response to the exercise intervention. There was no effect of exercise training on either t-PA release to SNP or endothelial release of plasminogen activator inhibitor-1. These initial results indicate that habitual aerobic exercise is an effective lifestyle intervention strategy for improving endothelial fibrinolytic capacity in HIV-1 infected adults.