Angiogenic growth factor expression in rat skeletal muscle in response to exercise training.
Angiogenesis occurs in skeletal muscle in response to exercise training. To gain insight into the regulation of this process, we evaluated the mRNA expression of factors implicated in angiogenesis over the course of a training program. We studied sedentary control (n = 17) rats and both sedentary (n = 18) and exercise-trained (n = 48) rats with bilateral femoral artery ligation. Training consisted of treadmill exercise (4 times/day, 1-24 days). 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 three- to sixfold increases in VEGF, VEGF receptors (KDR and Flt), the angiopoietin receptor (Tie-2), and endothelial nitric oxide synthase mRNA, which dissipated before the increase in capillarity, and a substantial (30- to 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 a sustained elevation of the angiopoietin 2-to-angiopoietin 1 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.
Lloyd
Pamela G
PG
Department of Biomedical Sciences, College of Veterinary Medicine, University of Missouri, 1600 E. Rollins Road, Columbia, MO 65211, USA.
Prior
Barry M
BM
Yang
Hsiao T
HT
Terjung
Ronald L
RL
D043925:Angiogenesis Inducing Agents / Q000235:genetics; D042683:Angiopoietin-1; D042702:Angiopoietin-2; D000818:Animals; D002196:Capillaries / Q000502:physiology; D018932:Chemokine CCL2 / Q000235:genetics; D016228:Endothelial Growth Factors / Q000235:genetics*; D015870:Gene Expression / Q000502:physiology; D036341:Intercellular Signaling Peptides and Proteins / Q000235:genetics*; D008026:Ligation; D008222:Lymphokines / Q000235:genetics*; D008297:Male; D008562:Membrane Glycoproteins / Q000235:genetics; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000502:physiology*; D018919:Neovascularization, Physiologic / Q000502:physiology; D019001:Nitric Oxide Synthase / Q000235:genetics; D052250:Nitric Oxide Synthase Type III; D010805:Physical Conditioning, Animal / Q000502:physiology*; D005082:Physical Exertion / Q000502:physiology*; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D020794:Receptor Protein-Tyrosine Kinases / Q000235:genetics; D042787:Receptor, TIE-2; D042461:Vascular Endothelial Growth Factor A; D040281:Vascular Endothelial Growth Factor Receptor-1 / Q000235:genetics; D040301:Vascular Endothelial Growth Factor Receptor-2 / Q000235:genetics; D042442:Vascular Endothelial Growth Factors
D043925:Angiogenesis Inducing Agents; D042683:Angiopoietin-1; D042702:Angiopoietin-2; C467629:Angpt1 protein, rat; D018932:Chemokine CCL2; D016228:Endothelial Growth Factors; D036341:Intercellular Signaling Peptides and Proteins; D008222:Lymphokines; D008562:Membrane Glycoproteins; D012333:RNA, Messenger; D042461:Vascular Endothelial Growth Factor A; D042442:Vascular Endothelial Growth Factors; D019001:Nitric Oxide Synthase; D052250:Nitric Oxide Synthase Type III; C496316:Nos3 protein, rat; D020794:Receptor Protein-Tyrosine Kinases; D042787:Receptor, TIE-2; D040281:Vascular Endothelial Growth Factor Receptor-1; D040301:Vascular Endothelial Growth Factor Receptor-2