title: The Notch pathway is a critical regulator of angiogenesis in a skin model of ischemia.
abstract: The Notch pathway is definitely required for normal vascular development. Although the contribution of Notch in postnatal angiogenesis is the focus of intense investigation, the implication of Notch in reparative neovascularization in the skin remains unexplored. In this study, we investigated Notch changes using a skin model of ischemia. Thirty Sprague-Dawley rats were divided into two groups. In the surgery group (n = 24), a caudally based dorsal skin flap was raised and sutured back into its initial position. In the control group, no surgical procedure was performed. Tissue biopsies were obtained at different time intervals. Tissue specimens were assessed for Delta-like ligand 4 (DLL4) and vascular endothelial growth factor (VEGF) gene expression by real-time polymerase chain reaction (PCR). Immunohistochemical staining was used for detection of DLL4 in tissue materials. Quantitative assessment of skin flap microvasculature was made. Compared with normoperfused tissue, VEGF and DLL4 expressions increased significantly (p < 0.01). Immunohistochemical analysis revealed weak and patchy expression of DLL4 in microvascular endothelial cells of normoperfused tissues. Conversely, DLL4 expression was upregulated in capillary endothelial cells after ischemia. In conclusion, in this study we have shown that the Notch ligand DLL4 is upregulated in skin tissue after ischemia. A deeper understanding of these fundamental principles will aid in the development of new avenues for the treatment of blood vessel-related skin pathologies.
authors.affiliation: Department of Plastic and Reconstructive Surgery, Ahi Evran University, Kirsehir, Turkey ozanluay@hotmail.com.
authors.forename: Ozan L
authors.initials: OL
authors.lastname: Abbas
authors.affiliation: Department of Plastic and Reconstructive Surgery, Başkent University, Ankara, Turkey.
authors.forename: Hüseyin
authors.initials: H
authors.lastname: Borman
authors.affiliation: Department of Medical Genetics, Başkent University, Ankara, Turkey.
authors.forename: Yunus K
authors.initials: YK
authors.lastname: Terzi
authors.affiliation: Department of Pathology, Başkent University, Ankara, Turkey.
authors.forename: Ayşen
authors.initials: A
authors.lastname: Terzi
authors.affiliation: Department of Biochemistry, Başkent University, Ankara, Turkey.
authors.forename: Nilüfer
authors.initials: N
authors.lastname: Bayraktar
authors.affiliation: Department of Biostatistics, Başkent University, Ankara, Turkey.
authors.forename: Ayşe C
authors.initials: AC
authors.lastname: Yazıcı
mesh_terms: D000818:Animals; D004195:Disease Models, Animal; D047908:Intracellular Signaling Peptides and Proteins / Q000502:physiology; D007511:Ischemia; D008297:Male; D008565:Membrane Proteins / Q000502:physiology; D018919:Neovascularization, Physiologic / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D051880:Receptors, Notch / Q000502:physiology*; D012867:Skin / Q000098:blood supply*; D042461:Vascular Endothelial Growth Factor A / Q000502:physiology
chemical_list: D047908:Intracellular Signaling Peptides and Proteins; D008565:Membrane Proteins; D051880:Receptors, Notch; D042461:Vascular Endothelial Growth Factor A; C064045:delta protein
keywords: Delta-like ligand; Notch pathway; angiogenesis