Exercise increases soluble vascular endothelial growth factor receptor-1 (sFlt-1) in circulation of healthy volunteers.
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.


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.
Bailey
Amelia Purser
AP
Department of Physiology & Biophysics, University of Mississippi Medical Center, Jackson, MS 39216-4505, USA.
Shparago
Megan
M
Gu
Jian-Wei
JW
D000328:Adult; D050197:Atherosclerosis / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D015444:Exercise / Q000502:physiology*; D005080:Exercise Test; D016222:Fibroblast Growth Factor 2 / Q000097:blood; D006801:Humans; D008297:Male; D009369:Neoplasms / Q000097:blood / Q000209:etiology / Q000517:prevention & control; D012307:Risk Factors; D012995:Solubility; D042461:Vascular Endothelial Growth Factor A / Q000037:antagonists & inhibitors / Q000097:blood; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000097:blood*
D042461:Vascular Endothelial Growth Factor A; D016222:Fibroblast Growth Factor 2; C501162:FLT1 protein, human; D040281:Vascular Endothelial Growth Factor Receptor-1