RESUMO
Inactivation of the VHL tumour suppressor gene is a highly frequent genetic event in the carcinogenesis of central nervous system-(CNS) hemangioblastomas (HBs). The patterning of the similar embryonic vasculogenesis is an increasing concern in HB-neovascularization, and the classic vascular endothelial growth factor (VEGF)-mediated angiogenesis driven by VHL loss-of-function from human endothelium have been questioned. With this regard, we identify a distinct, VHL silencing-driven mechanism in which human vascular endothelial cells by means of increasing cell proliferation and decreasing cell apoptosis, is concomitant with facilitating accumulation of Twist1 protein in vascular endothelial cells in vitro. Importantly, this molecular mechanism is also pinpointed in CNS-HBs, and associated with the process of HB-neovascularization. In contrast with recent studies of HB-neovascularization, these modified cells did not endow with the typical features of vasculogenesis, indicating that this is a common angiogenesis implementing the formation of the vascular network. Taken together, these findings suggest that vasculogenesis and angiogenesis may constitute complementary mechanisms for HB-neovascularization, and could provide a rational recognition of single anti-angiogenic intervention including targeting to the Twist1 signalling for HBs.
Assuntos
Neoplasias Cerebelares/genética , Regulação Neoplásica da Expressão Gênica , Hemangioblastoma/genética , Neovascularização Patológica/genética , Proteínas Nucleares/genética , Proteína 1 Relacionada a Twist/genética , Proteína Supressora de Tumor Von Hippel-Lindau/genética , Adolescente , Adulto , Idoso , Apoptose , Ciclo Celular/genética , Linhagem Celular Tumoral , Proliferação de Células , Neoplasias Cerebelares/irrigação sanguínea , Neoplasias Cerebelares/metabolismo , Neoplasias Cerebelares/patologia , Feminino , Perfilação da Expressão Gênica , Ontologia Genética , Células HEK293 , Hemangioblastoma/irrigação sanguínea , Hemangioblastoma/metabolismo , Hemangioblastoma/patologia , Células Endoteliais da Veia Umbilical Humana/citologia , Células Endoteliais da Veia Umbilical Humana/metabolismo , Humanos , Masculino , Pessoa de Meia-Idade , Anotação de Sequência Molecular , Neovascularização Patológica/metabolismo , Neovascularização Patológica/patologia , Proteínas Nucleares/metabolismo , Isoformas de Proteínas/antagonistas & inibidores , Isoformas de Proteínas/genética , Isoformas de Proteínas/metabolismo , RNA Interferente Pequeno/genética , RNA Interferente Pequeno/metabolismo , Transdução de Sinais , Proteína 1 Relacionada a Twist/metabolismo , Proteína Supressora de Tumor Von Hippel-Lindau/antagonistas & inibidores , Proteína Supressora de Tumor Von Hippel-Lindau/metabolismoRESUMO
OBJECTIVE: To study the changes of cat cerebral microcirculation in early stage after craniocerebral gunshot wound in the hot and humid environment to provide laboratory evidence for clinical treatment of such wound. METHODS: Craniocerebral gunshot wound was induced in 24 cats according to the method described by Carey with modifications, and the cats were placed in a cabin with environmental temperature and humidity of 25 degrees Celsius and 50% (group A), and 35 degrees Celsius and 85% (group B), respectively, to observe the changes in all the indices of cerebral microcirculation. RESULTS: All the cats survived and notable changes occurred in the morphology and permeability of cerebral microvascular along with obvious pathological changes in the brain tissue, and the vital signs, hemorheology and blood-brain barrier were significantly different between groups A and B. CONCLUSION: Hot and humid environment induces obvious changes in cat cerebral microcirculation and blood-brain barrier function in the early stages after craniocerebral gunshot wound.
