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1 Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA
2 Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, Columbia, Missouri, USA; Department of Physiology, College of Medicine, University of Missouri, Columbia, Missouri, USA; Dalton Cardiovascular Research Center, University of Missouri, Columbia, Missouri, USA
* To whom correspondence should be addressed. E-mail: terjungr{at}missouri.edu.
Angiogenesis occurs in skeletal muscle in response to exercise training. To gain insight into the regulation of this process, we evaluated mRNA expression of factors implicated in angiogenesis over the course of a training program. We studied sedentary control (CONT, n=17) and both sedentary (LIG, n=18) and exercise-trained (LIG-EX, n=48) rats with bilateral femoral artery ligation. Training consisted of treadmill exercise (4x/day, 1-24 d). Basal mRNA expression in sedentary control muscle was inversely related to muscle vascularity. Angiogenesis was histologically evident in trained white gastrocnemius muscle by day 12. Training produced initial 3-6 fold increases in vascular endothelial growth factor (VEGF), VEGF receptors (KDR, Flt), the angiopoietin (Ang) receptor (Tie-2), and endothelial nitric oxide synthase (eNOS) mRNA, which dissipated prior to the increase in capillarity, and a substantial (30-50 fold) but transient upregulation of monocyte chemoattractant protein-1 mRNA. These results emphasize the importance of early events in regulating angiogenesis. However, we observed sustained elevation of the Ang2:Ang1 ratio, suggesting continued vascular destabilization. The response to exercise was (in general) tempered in high-oxidative muscles. These findings place importance on cellular events coupled to the onset of angiogenesis.
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