Background: Physical inactivity increases the risk of cancer and atherosclerosis; the impaired regulation of angiogenesis is often associated with the development of these diseases. We hypothesize that exercise increases circulating sFlt-1, an endogenous VEGF inhibitor, which may functionally decrease plasma levels of free VEGF.

Material/methods: 5 healthy male adults were assigned to a treadmill exercise study. The peak speed and the time spent at peak speed on the treadmill were 4.8+/-1.0 miles/h and 6.8+/-2.6 minutes, respectively. Plasma levels of sFlt-1 and VEGF were determined using ELISA (R&D Systems).

Results: Basal plasma levels of sFlt-1 (before exercise) were 48.8+/-9.0 pg/ml. Plasma levels of sFlt-1 increased to 72.9+/-14.6 pg/ml at 0.5 h after exercise, compared to the basal levels (49% higher, P=0.0048). The plasma levels then returned to 47.5+/-14.3 and 43.3+/-10.2 pg/ml, at 2 and 6 h after exercise, respectively. There was a significant positive correlation between % increase in plasma levels of sFlt-1 and total peak oxygen consumption during exercise (R2=0.8244; P<0.01). Basal plasma levels of unbound VEGF were 37.3+/-7.7 pg/ml, then decreased to 28.2+/-6.3, 17.5+/-2.5, and 26.6+/-6.4 pg/ml, at 0.5, 2, and 6 h, respectively, after exercise. There was a significant increase in basal plasma levels of sFlt-1 after repeated exercise for 2 weeks.

Conclusions: We have demonstrated that circulating sFlt-1 is significantly increased by exercise in healthy volunteers, which is functionally associated with a transient decrease in circulating free VEGF. This data may provide new insight into the molecular links between physical inactivity and risk of cancer and atherosclerosis.