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1 Integrative Physiology, University of Colorado, Boulder, Colorado, USA
2 Integrative Physiology, University of Colorado, Boulder, Colorado, USA; Department of Medicine, University of Colorado Health Sciences Center, Denver, Colorado, USA
* To whom correspondence should be addressed. E-mail: desouzac{at}colorado.edu.
Endothelial release of tissue-type plasminogen activator (t-PA) regulates fibrinolysis and is considered
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 (< 25 kg/m2); 22 overweight (BMI 
25 < 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 and sodium nitroprusside. Second, we studied 17 overweight and obese adults
who completed a 3-month 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/min) and obese
(0.1± 0.6 to 47.7±5.2 ng/100 mL tissue/min) compared with normal weight (0.1±0.8 to 77.5±6.7 ng/100 mL tissue/min) 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/min before training vs 1.0±0.9 to 65.4±6.3 ng/100 mL tissue/min after training) to levels comparable to those of their normal weight peers. These results indicate that overweight and obesity is 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.
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