5 All cases of FNH and HCA that were included in our present study were categorized according SB525334 chemical structure to their immunophenotypes. Although our study was focused on the possible role of the angiopoietins in the development of the vascular lesions of FNH and HCA and not on the classification of the lesions, our findings of increased Ang-1 in FNH and HCA are in line with the aforementioned studies. The most characteristic vascular features of FNH are the thick-walled vessels with myointimal hyperplasia located in the central scar

and in the radiating septa, and they exist next to the periseptal sinusoidal enhanced α-SMA and CD34 expression, which is indicative of sinusoidal capillarization and vascular remodeling.20, 21 The increased

expression of Ang-1 and Tie-2 without a concurrent increase in Ang-2 expression creates a condition that can facilitate Ang-1/Tie-2 signaling. Among other things, this can lead to recruitment of SMCs and promotion of differentiation of mesenchymal cells into vascular SMCs.22, 23 Gain-of-function studies have shown that prolonged expression or overexpression of Ang-1 results in various vascular abnormalities, including larger, more numerous, and highly branched vessels in the skin, vascular enlargement in hepatic microvascular remodeling, and cardiac allograft vasculopathy, which are all dysmorphic MAPK Inhibitor Library vascular changes that resemble the vascular features found in FNH and HCA.14, 15, 24, 25 In cardiac graft vasculopathy, inflammation and arterial injury initiate subsequent myointimal proliferation. Transgenic overexpression of both Ang-1 and Ang-2 decrease inflammation, whereas induced Ang-1 expression (not Ang-2) stimulates activation of vascular SMCs, which results in myointimal growth and development of cardiac vasculopathy.25 It is conceivable that in FNH, overexpression of Ang-1 and a relative lack of Ang-2 lead to a similar course of action. Within the context of the assumed primary vascular injury, the dominant Ang-1 overexpression in FNH, which is emphasized by the significantly enhanced Ang-1/Ang-2

ratio, might stimulate excessive recruitment of vascular 上海皓元 SMCs and elicit myointimal hyperplasia. As a result, the dystrophic vessels characteristic of FNH can form. The subsequent compromised vascular supply may underlie local hemodynamic changes leading to regenerative parenchymal hyperplasia; this finding is similar to the FNH-like nodules in mouse livers under the influence of overexpression of Ang-1.14 Also, the occurrence of other vascular abnormalities found in HCA and FNH is supportive of the concept that they are related to excessive Ang-1 activity. In the studies of transgenic expression of Ang-1 in hepatocytes, a spectrum of hepatic vascular changes were documented, and they consisted of arterial sprouting, loss of portal triads, peliotic changes, and vessel dilatation.