Angiogenesis in chronic inflammatory liver disease

Abstract

Intrahepatic hypoxia may occur during the inflammatory and fibrotic processes that characterize several chronic liver diseases of viral and autoimmune origin. As a consequence, new vascular structures are formed to provide oxygen and nutrients. Angiogenesis involves a tightly regulated network of cellular and molecular mechanisms that result in the formation of functional vessels. Of particular importance are growth factors, molecules involved in matrix remodeling and cell migration, and vessel maturation-related factors. In recent years, a number of studies have examined the expression and function of many pro-and antiangiogenic molecules in the setting of nontumoral chronic liver diseases and liver regeneration. This review examines the potential pathogenetic role of angiogenesis in the context of viral hepatitis, cirrhosis, autoimmune hepatitis, primary biliary cirrhosis, and alcoholic liver disease. The future perspectives for research in this field are outlined.

Simultaneous characterization of progenitor cell compartments in adult human liver

“…The morphology and phenotype of the CD146 1 /KDR 1 /CD31 1 /CD144 1 /CD45 2 cell population were similar to those of circulating ECFCs, the only subpopulation capable of forming vessels in vivo (16). They were more frequent in patients than in donors, which is in line with the current view that hepatic inflammation and fibrogenesis are frequently associated with angiogenesis (29).…”

Differential Roles of Angiogenesis in the Induction of Fibrogenesis and the Resolution of Fibrosis in Liver

“…4,15) HIF-1α then activates the transcription of genes such as VEGF, which are directly or indirectly involved in angiogenesis. 15,16) VEGF is a major regulator of vascular formation and remodeling through effects on EC activation and proliferation.…”

“…4,15) HIF-1α then activates the transcription of genes such as VEGF, which are directly or indirectly involved in angiogenesis. 15,16) VEGF is a major regulator of vascular formation and remodeling through effects on EC activation and proliferation. 17) VEGF is mediated via two tyrosine kinase receptors, VEGF receptor 1 (VEGFR-1, Flt-1) and VEGFR-2 (KDR, Flk-1), which are mainly expressed on EC.…”

Overexpression of Notch1 Ectodomain in Myeloid Cells Induces Vascular Malformations through a Paracrine Pathway

“…To determine whether the vascular malformations of embryonic liver were a prerequisite for the development of the adult liver disease, we took advantage of the ability of the liver to regenerate after hepatectomy as a model of liver angiogenesis. 25 Two-month-old adult mice were subjected to partial hepatectomy and sacrificed 20 days later. In each Tg mouse assessed (n ϭ 5), the regenerated lobule was found to be smaller than the non-Tg one (n ϭ 4) ( Figure 4I) and to show severe vascular malformations (including large vessels crawling at its surface, decreased branching, and clustered capillaries sprouting from them) (Figure 4, I [d] and M), even more severe than those observed in the nonhepactectomized lobules of the same Tg mouse ( Figure 4L).…”