RESUMO
PURPOSE OF REVIEW: The decreasing postoperative mortality in patients with congenital heart disease has enabled an increasing interest in preventing morbidity, especially from the central nervous system. Near-infrared spectroscopy, a noninvasive technology that provides an estimate of tissue oxygenation, has been introduced in the intensive care unit and has gained popularity over the last decade. This review aims to ascertain its ability to affect outcome. RECENT FINDINGS: Recent studies have started to incorporate cerebral near-infrared spectroscopy in the assessment, evolution, and outcomes of surgical patients with congenital heart disease. These studies often represent small single-center high-risk cohorts that are evaluated in a retrospective or an observational manner. Nevertheless, new data are starting to indicate that near-infrared spectroscopy may be helpful not only in the assessment of critical care parameters, such as cardiac output performance or likelihood of adverse events, but, most notably, in the long-term neurological outcome. SUMMARY: In addition to additional corroborative trials from different centers, a critical question that remains to be answered is whether targeting cerebral near-infrared spectroscopy values, as part of goal-directed therapy protocols, can help to improve outcome overall.
Assuntos
Cuidados Críticos , Cardiopatias Congênitas/fisiopatologia , Monitorização Fisiológica/métodos , Fluxo Pulsátil , Fluxo Sanguíneo Regional , Espectroscopia de Luz Próxima ao Infravermelho , Criança , Pré-Escolar , Cardiopatias Congênitas/mortalidade , Humanos , Unidades de Terapia Intensiva Pediátrica , Valor Preditivo dos TestesRESUMO
Here, we demonstrate that carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is expressed and co-localized with podoplanin in lymphatic endothelial cells (LECs) of tumor but not of normal tissue. CEACAM1 overexpression in human dermal microvascular endothelial cells (HDMECs) results in a significant increase of podoplanin-positive cells in fluorescence-activated cell sorting analyses, while such effects are not observed in CEACAM1 overexpressing human umbilical vein endothelial cell (HUVECs). This effect of CEACAM1 is ceased when HDMECs are transfected with CEACAM1/y- missing the tyrosine residues in its cytoplasmic domain. CEACAM1 overexpression in HDMECs leads to an up-regulation of vascular endothelial growth factor C, -D (VEGF-C, -D) and their receptor vascular endothelial growth factor receptor 3 (VEGFR-3) at mRNA and protein levels. HDMECs transfected with CEACAM1 but not those with CEACAM1/y- show enhanced expression of the lymphatic markers Prox1, podoplanin, and LYVE-1. Furthermore, Prox1 silencing in HDMECs via small interfering RNA blocks the CEACAM1-induced increase of VEGFR-3 expression. Number and network of endothelial tubes induced by VEGF-C and -D are enhanced in CEACAM1-overexpressing HDMECs. Moreover, VEGF-A treatment of CEACAM1-silenced HDMECs restores their survival but not that with VEGF-C and VEGF-D. These data imply that the interaction of CEACAM1 with Prox1 and VEGFR-3 plays a crucial role in tumor lymphangiogenesis and reprogramming of vascular endothelial cells to LECs. CEACAM1-induced signaling effects appear to be dependent on the presence of tyrosine residues in the CEACAM1 cytoplasmic domain.
Assuntos
Antígenos CD/fisiologia , Moléculas de Adesão Celular/fisiologia , Endotélio Linfático/citologia , Endotélio Vascular/citologia , Proteínas de Homeodomínio/metabolismo , Linfangiogênese , Proteínas Supressoras de Tumor/metabolismo , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/metabolismo , Antígenos CD/genética , Antígenos CD/metabolismo , Moléculas de Adesão Celular/genética , Moléculas de Adesão Celular/metabolismo , Linhagem da Célula , Células Cultivadas , Células Endoteliais/citologia , Proteínas de Homeodomínio/genética , Humanos , Glicoproteínas de Membrana/genética , Glicoproteínas de Membrana/metabolismo , Microcirculação , Ligação Proteica , RNA Mensageiro/análise , Pele/irrigação sanguínea , Proteínas Supressoras de Tumor/genética , Veias Umbilicais/citologia , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/análise , Receptor 3 de Fatores de Crescimento do Endotélio Vascular/genética , Fatores de Crescimento do Endotélio Vascular/análise , Fatores de Crescimento do Endotélio Vascular/genéticaRESUMO
Here, we demonstrate the expression of carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) in angiogenic sprouts but not in large mother blood vessels within tumor tissue. Correspondingly, only human microvascular endothelial cells involved in in vitro tube formation exhibit CEACAM1. CEACAM1-overexpressing versus CEACAM1-silenced human microvascular endothelial cells were used in migration and tube formation assays. CEACAM1-overexpressing microvascular endothelial cells showed prolonged survival and increased tube formation when they were stimulated with vascular endothelial growth factor (VEGF), whereas CEACAM1 silencing via small interfering RNA blocks these effects. Gene array and LightCycler analyses show an up-regulation of angiogenic factors such as VEGF, VEGF receptor 2, angiopoietin-1, angiopoietin-2, tie-2, angiogenin, and interleukin-8 but a down-regulation of collagen XVIII/endostatin and Tie-1 in CEACAM1-overexpressing microvascular endothelial cells. Western blot analyses confirm these results for VEGF and endostatin at the protein level. These results suggest that constitutive expression of CEACAM1 in microvascular endothelial cells switches them to an angiogenic phenotype, whereas CEACAM1 silencing apparently abrogates the VEGF-induced morphogenetic effects during capillary formation. Thus, strategies targeting the endothelial up-regulation of CEACAM1 might be promising for antiangiogenic tumor therapy.
Assuntos
Antígenos CD/fisiologia , Antígenos de Diferenciação/fisiologia , Endotélio Vascular/fisiologia , Neovascularização Fisiológica/fisiologia , Transdução de Sinais/fisiologia , Sequência de Bases , Moléculas de Adesão Celular , Sobrevivência Celular/fisiologia , Células Cultivadas , Colágeno Tipo XVIII/fisiologia , Primers do DNA , Regulação para Baixo/fisiologia , Endostatinas/fisiologia , Endotélio Vascular/citologia , Humanos , Receptor de TIE-1/fisiologiaRESUMO
Carcinoembryonic antigen-related cell adhesion molecule-1 (CEACAM1) is usually expressed at the luminal surface of different epithelia and is up-regulated in endothelial cells during angiogenesis. Here, we demonstrate evidence of morphogenetic effects of CEACAM1 in spermatogenesis. CEACAM1 is detectable in normal testicular tissue and seminal fluid. It is present in the adluminal part of Sertoli cells extending only as far as the tight junctions between them. CEACAM1 immunostaining is significantly increased and extends to the basal part of Sertoli cells in the presence of carcinoma in situ. Also, in vitro-induced spermatogenetic disturbance leads to an enhanced CEACAM1 expression in Sertoli cells after 3 days of culture. Remarkably, seminiferous tubules containing exclusively Sertoli cells do not exhibit any CEACAM1 expression. CEACAM1 staining was absent in vascular endothelial cells of normal testicular tissue, but present in small blood vessels of seminomas. These data suggest that CEACAM1 expression in Sertoli cells depends on the presence of germ cells and plays a role in adhesive interactions between Sertoli and differentiating germ cells. Its up-regulation in Sertoli cells accompanying spermatogenic damage may contribute to reconstruction and maintenance of the tubular structure of seminiferous tubules. Additionally, CEACAM1 is apparently involved in the angiogenesis of germ cell tumours.