Heparin and angiogenesis: a low-molecular-weight fraction inhibits and a high-molecular-weight fraction stimulates angiogenesis systemically.
The systemic effect of 2.4-, 8-, 15- and 22-kDa heparin fractions on saline-mediated angiogenesis in rats was compared with the systemic effect of an unfractionated Na-standard heparin (UFH), which had a mean molecular weight of about 15 kDa. Using the mesenteric-window assay in adult rats, the relative vascularized area was quantified morphometrically. The angiogenic response was strictly related to the mean molecular weight of the saccharides (r = 0.97); the 2.4-kDa fraction suppressed angiogenesis by 46% (p < or = 0.001), whereas the 22-kDa fraction stimulated angiogenesis by 123% (p < or = 0.01), as compared with the UFH. The UFH, thus, contained chain-length-related fragments that induced systemic antiangiogenic and angiogenic activity.
Norrby
K
K
Department of Pathology, University of Göteborg, Sahlgren Hospital, Sweden.
D000818:Animals; D016220:Fibroblast Growth Factor 1 / Q000378:metabolism; D016222:Fibroblast Growth Factor 2 / Q000378:metabolism; D006493:Heparin / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D006495:Heparin, Low-Molecular-Weight / Q000008:administration & dosage / Q000494:pharmacology* / Q000633:toxicity; D007279:Injections, Subcutaneous; D008297:Male; D008643:Mesentery / Q000098:blood supply; D008970:Molecular Weight; D009389:Neovascularization, Pathologic / Q000139:chemically induced* / Q000517:prevention & control*; D009844:Oligosaccharides / Q000008:administration & dosage / Q000494:pharmacology / Q000633:toxicity; D051381:Rats; D017207:Rats, Sprague-Dawley; D012965:Sodium Chloride / Q000633:toxicity
D006495:Heparin, Low-Molecular-Weight; D009844:Oligosaccharides; D016222:Fibroblast Growth Factor 2; D016220:Fibroblast Growth Factor 1; D012965:Sodium Chloride; D006493:Heparin