title: Chronic delivery of a thrombospondin-1 mimetic decreases skeletal muscle capillarity in mice.
abstract: Angiogenesis is an essential process for normal skeletal muscle function. There is a growing body of evidence suggesting that thrombospondin-1 (TSP-1), a potent antiangiogenic protein in tumorigenesis, is an important regulator of both physiological and pathological skeletal muscle angiogenesis. We tested the hypothesis that chronic exposure to a TSP-1 mimetic (ABT-510), which targets the CD36 TSP-1 receptor, would decrease skeletal muscle capillarity as well as alter the balance between positive and negative angiogenic proteins under basal conditions. Osmotic minipumps with either ABT-510 or vehicle (5% dextrose) were implanted subcutaneously in the subscapular region of C57/BL6 mice for 14 days. When compared to the vehicle treated mice, the ABT-510 group had a 20% decrease in capillarity in the superficial region of the gastrocnemius (GA), 11% decrease in the plantaris (PLT), and a 35% decrease in the soleus (SOL). ABT-510 also decreased muscle protein expression of vascular endothelial growth factor (VEGF) in both the GA (-140%) and SOL (-62%); however there was no change in VEGF in the PLT. Serum VEGF was not altered in ABT-510 treated animals. Endogenous TSP-1 protein expression in all muscles remained unaltered. Tunnel staining revealed no difference in muscle apoptosis between ABT-510 and vehicle treated groups. These data provide evidence that the anti-angiogenic effects of TSP-1 are mediated, at least in part, via the CD36 receptor. It also suggests that under physiologic conditions the TSP-1/CD36 axis plays a role in regulating basal skeletal muscle microvessel density.
authors: Division of Exercise Physiology, Center for Cardiovascular and Respiratory Sciences, West Virginia University School of Medicine, Morgantown, West Virginia, United States of America.
authors: Gerald N
authors: GN
authors: Audet
authors: Daniel
authors: D
authors: Fulks
authors: Janelle C
authors: JC
authors: Stricker
authors: I Mark
authors: IM
authors: Olfert
mesh_terms: D000818:Animals; D017209:Apoptosis; D040761:Biomimetic Materials / Q000008:administration & dosage*; D018955:CD36 Antigens / Q000378:metabolism; D002197:Capillary Action / Q000187:drug effects*; D016503:Drug Delivery Systems; D004797:Enzyme-Linked Immunosorbent Assay; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D018482:Muscle, Skeletal / Q000098:blood supply* / Q000187:drug effects / Q000473:pathology; D018919:Neovascularization, Physiologic / Q000187:drug effects*; D009842:Oligopeptides / Q000008:administration & dosage* / Q000494:pharmacology; D010805:Physical Conditioning, Animal; D012420:Running; D019700:Thrombospondin 1 / Q000378:metabolism*; D042461:Vascular Endothelial Growth Factor A / Q000378:metabolism
chemical_list: D018955:CD36 Antigens; C500617:NAc-Sar-Gly-Val-(d-allo-Ile)-Thr-Nva-Ile-Arg-ProNEt; D009842:Oligopeptides; D019700:Thrombospondin 1; D042461:Vascular Endothelial Growth Factor A; C467480:vascular endothelial growth factor A, mouse