RESUMO
BACKGROUND & AIMS: Chronic injury changes the fate of certain cellular populations, inducing epithelial cells to generate fibroblasts by epithelial-to-mesenchymal transition (EMT) and mesenchymal cells to generate epithelial cells by mesenchymal-to-epithelial transition (MET). Although contribution of EMT/MET to embryogenesis, renal fibrosis, and lung fibrosis is well documented, role of EMT/MET in liver fibrosis is unclear. We determined whether cytokeratin-19 positive (K19(+)) cholangiocytes give rise to myofibroblasts (EMT) and/or whether glial fibrillary acidic protein positive (GFAP(+)) hepatic stellate cells (HSCs) can express epithelial markers (MET) in response to experimental liver injury. METHODS: EMT was studied with Cre-loxP system to map cell fate of K19(+) cholangiocytes in K19(YFP) or fibroblast-specific protein-1 (FSP-1)(YFP) mice, generated by crossing tamoxifen-inducible K19(CreERT) mice or FSP-1(Cre) mice with Rosa26(f/f-YFP) mice. MET of GFAP(+) HSCs was studied in GFAP(GFP) mice. Mice were subjected to bile duct ligation or CCl(4)-liver injury, and livers were analyzed for expression of mesodermal and epithelial markers. RESULTS: On Cre-loxP recombination, >40% of genetically labeled K19(+) cholangiocytes expressed yellow fluorescent protein (YFP). All mice developed liver fibrosis. However, specific immunostaining of K19(YFP) cholangiocytes showed no expression of EMT markers alpha-smooth muscle actin, desmin, or FSP-1. Moreover, cells genetically labeled by FSP-1(YFP) expression did not coexpress cholangiocyte markers K19 or E-cadherin. Genetically labeled GFAP(GFP) HSCs did not express epithelial or liver progenitor markers in response to liver injury. CONCLUSION: EMT of cholangiocytes identified by genetic labeling does not contribute to hepatic fibrosis in mice. Likewise, GFAP(Cre)-labeled HSCs showed no coexpression of epithelial markers, providing no evidence for MET in HSCs in response to fibrogenic liver injury.
Assuntos
Transdiferenciação Celular , Doença Hepática Induzida por Substâncias e Drogas/patologia , Células Epiteliais/patologia , Fibroblastos/patologia , Cirrose Hepática/patologia , Regeneração Hepática , Fígado/patologia , Animais , Ductos Biliares/cirurgia , Biomarcadores/metabolismo , Proteínas de Ligação ao Cálcio/genética , Tetracloreto de Carbono , Linhagem da Célula , Transdiferenciação Celular/genética , Doença Hepática Induzida por Substâncias e Drogas/genética , Doença Hepática Induzida por Substâncias e Drogas/metabolismo , Colágeno Tipo II/genética , Cruzamentos Genéticos , Modelos Animais de Doenças , Células Epiteliais/metabolismo , Fibroblastos/metabolismo , Genes Reporter , Proteína Glial Fibrilar Ácida/genética , Células Estreladas do Fígado/patologia , Imuno-Histoquímica , Queratina-19/genética , Ligadura , Fígado/metabolismo , Cirrose Hepática/genética , Cirrose Hepática/metabolismo , Regeneração Hepática/genética , Proteínas Luminescentes/biossíntese , Proteínas Luminescentes/genética , Camundongos , Camundongos Transgênicos , Regiões Promotoras Genéticas , Proteínas/genética , RNA não Traduzido , Proteína A4 de Ligação a Cálcio da Família S100 , Proteínas S100RESUMO
BACKGROUND: Patient satisfaction after percutaneous endovascular procedures is significantly influenced by the amount of time to ambulation postprocedure. The purpose of this study was to assess the complication rates of early ambulation after use of closure devices or topical hemostatic agents for femoral access sites for endovascular procedures. METHODS: A retrospective review was performed of all patients who underwent an endovascular procedure from a femoral access site between January 2004 and March 2008. The access site was closed with an Angio-Seal, StarClose, or D-Stat Dry with pressure. Patients ambulated 2 hr postprocedure when a closure device was used and 4 hr postprocedure when a D-Stat pad was applied. Access-site bleeding complications were assessed. Sheath size, closure method, patient characteristics, and antiplatelet status were analyzed. RESULTS: A total of 245 patients with a mean age of 70 years were identified. Of these, 154 (63%) patients were treated with a D-Stat pad with pressure, Angio-Seal was used on 83 (34%), and StarClose was used on eight (3%). The overall complication rate was 5.7%. Complications increased with increasing age (p = 0.003) and use of StarClose (p = 0.0001). The D-Stat pad was associated with a decreased complication rate (p = 0.03). Sheath size did not influence the incidence of bleeding. There was no significant increase in complications in patients taking an antiplatelet agent. CONCLUSION: With a protocol using closure devices and hemostatic agents, early ambulation after percutaneous femoral access can be achieved safely with an acceptable complication rate in patients with peripheral vascular disease.