Angiogenesis is the process whereby new blood vessels sprout from existing vessels and requires that the specialized resident cells lining the vasculature, the endothelial cells (ECs), proliferate, migrate and differentiate spatially and temporally in response to specific signals. Vasculogenesis, on the other hand, has only recently emerged as an alternative mechanism of blood vessel growth in adult tissues and is the result of homing and engraftment of circulating EC precursors (ECPs) of bone marrow origin to sites of neovascularization. Both events are known to occur within the liver vasculature under very different conditions of growth, injury and repair, but the extent of each and the mechanisms by which they occur for each case is completely unknown. We evaluate the growth factor signaling events that accompany blood vessel growth and repair during liver regeneration following partial hepatectomy, and as the result of ischemia/reperfusion injury following liver transplantation. Comparative analysis of these two systems will elucidate both similar and dissimilar mechanisms that control these events and potentially lead to optimization of therapies that will reflect the specific requirements for injury based neovascularization in the liver.
- Tomiyama, K, N Murase, DB Stolz, H Toyokawa, DR O'Donnell, DM Smith, JR Dudas, JR Rubin, KG Marra. Stem Cells In Press.
- Stolz, DB, MA Ross, A Ikeda, K Tomiyama, T Kaizu, DA Geller, N Murase. Sinusoidal endothelial cell repopulation following ischemia/reperfusion injury in rat liver transplantation. Hepatology 46:1464-1475. 2007
- Khan, Z, GK Michalopoulos, DB Stolz. Peroxisomal localization of hypoxia-inducible factors and HIF regulatory hydroxylases in primary rat hepatocytes exposed to hypoxia-reoxygenation American Journal of Pathology 126(4):1251-1269. 2006.
- Stolz DB, R Zamora, Y Vodovotz, PA Loughan, Y-M Kim, TR Billiar, RL Simmons, SC Watkins. Peroxisomal localization of inducible nitric oxide synthase in rat hepatocytes Hepatology 36:81-93. 2002.
- Ross MA, CM Sander, TB Kleeb, SC Watkins, DB Stolz. Spatiotemporal expression of angiogenesis growth factor receptors during the revascularization of regenerating rat liver. Hepatology 34:1135-1148. 2001.
- Wack KE, MA Ross, V Zegarra, SC Watkins, DB Stolz. Sinusoidal ultrastructure evaluated during the revascularization of regenerating rat liver. Hepatology 33:363-378. 2001.
- Stolz DB, MA Ross, HM Salem, W M Mars, GK Michalopoulos, K Enomoto. Cationic Colloidal Silica Membrane Perturbation as a Means of Examining Changes at the Sinusoidal Surface During Liver Regeneration. American Journal of Pathology 155:1487-1498. 1999.
- Stolz DB, WM Mars, BE Petersen, T-H Kim, GK Michalopoulos. Growth factor signal transduction immediately following two-thirds partial hepatectomy in the rat. Cancer Research 59:3954-3960. 1999.
- Jacobson, B.S., DB Stolz & JE Schnitzer. Identification of endothelial cell surface proteins as potential targets for diagnosis and disease. Nature Medicine 2(4)482-484. 1996
- Stolz DB & BS Jacobson. Examination of transcellular membrane protein polarity of bovine aortic endothelial cells in vitrousing the cationic colloidal silica microbead isolation procedure. Journal of Cell Science 103, 39-51. 1992.
University of Pittsburgh
Department of Cell Biology