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.