The parallel findings also extend to the dilated sinusoids and peliotic changes, which are regular features of HCA and FNH. Arterial sprouts, described in Ang-1 transgenic mice, might well represent the equivalent of the single arteries
that are regularly found in HCA. The large dystrophic vessels with robust myointimal thickening that characterize FNH are, however, not found in HCA. These differences indicate a preponderance of the myofibroblast BMN 673 price recruitment effect of Ang-1 in FNH, whereas in HCA, up-regulation of Ang-1 seems to be predominantly stimulating vascular remodeling. These variable effects of Ang-1 could be due to the difference in the magnitude of Ang-1 enhancement, although the etiological context in which Ang-1 exerts its effects is probably similar if not more important. BMS-907351 research buy The etiological
context of FNH is a liver already affected by vascular injury that possibly has stimulated reparative mechanisms to restore vascular integrity and triggered recruitment of vascular SMCs. Of note is the fact that the nodular lesions resembling human FNH in the hepatic Ang-1 transgenic mice were also preceded by an obliterative vascular lesion.14 It remains to be elucidated whether the early stage of vascular injury itself provokes Ang-1 overexpression in FNH. HCA is
a primary neoplastic lesion and lacks a primary vascular anomaly such as that in FNH. As such, in HCA, the vascular integrity is not jeopardized, and recruitment of myofibroblasts to stabilize vessels is less stimulated; this is compatible with the less prominent increase in Ang-1 observed in HCA. The emphasis of Ang-1 overexpression in HCA seems to lie in the induction of vascular remodeling. Whether these vascular changes represent angiogenesis effective at providing neoplastic growth with its increasing vascular demands is yet unclear. The single arteries observed in HCA are also regularly else found in HCC, and in our previous study, we also found increased Ang-1 in human HCC.8 However, studies on the expression of Ang-1 in tumor models have reported variable results in different types of tumors, including the induction of tumor angiogenesis in astrocytomas, glioblastomas, and cervical cancer but a decrease in angiogenesis in colorectal cancer and liver metastases of colorectal cancer (reviewed by Shim et al.26). In conclusion, we have demonstrated increased expression of the angiogenic growth factor Ang-1 in FNH and HCA with maintenance of the expression of its receptor Tie-2, which potentially underlies the development of the dysmorphic vascular features in these two lesions.