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1 Department of Laboratory Medicine, Section of Clinical Physiology, Karolinska Institute, Stockholm, Sweden
2 Department of Physiology and Pharmacology, Karolinska Institute, Sweden; Department of Molecular Biology, Karolinska Institute, Sweden
3 Department of Laboratory Medicine, Section of Clinical Physiology, Karolinska Institute, Stockholm, Sweden; Department of Physiology and Pharmacology, Karolinska Institute, Sweden
4 Dept of Physiology and Pharmacology, Karolinska Institutet, 171 77 Stockholm, Sweden
* To whom correspondence should be addressed. E-mail: thomas.gustafsson{at}ki.se.
Eleven subjects performed one-legged exercise four times per week for five weeks. The subjects exercised one leg for 45 min with restricted blood flow (R-leg), followed by exercise with the other leg at the same absolute workload with unrestricted blood flow (UR-leg). mRNA and protein expression were measured in biopsies from the vastus lateralis muscle obtained at rest before the training period, after 10 days and after five weeks of training as well as 120 minutes after the first and last exercise bouts. Basal Ang-2 and Tie-1 mRNA levels increased in both legs with training. The Ang-2:Ang-1 ratio increased to a greater extent in the R-leg. The changes in Ang-2 mRNA were followed by similar changes at the protein level. In the R-leg, VEGF-A mRNA expression responded transiently after acute exercise both before and after the five-week training program. Over the course of the exercise program, there was a concurrent increase in basal VEGF-A protein and VEGFR-2 mRNA in the R-leg. Ki67 mRNA showed a greater increase in the R-leg and the protein was localized to the endothelial cells. In summary, the increased translation of VEGF-A is suggested to be caused by the short mRNA burst induced by each exercise bout. The concurrent increase in the Ang-2:Ang-1 ratio and the VEGF-expression combined with the higher level of Ki67 mRNA in the R-leg indicate that changes in these systems are of importance also in non-pathological angiogenic condition such as voluntary exercise in humans.
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