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Disruption of the integrity of vascular endothelium plays an essential role in the development and the progression of numerous human diseases, including sepsis, atherosclerosis and others. A complex array of transmembrane adhesive proteins located in junctional structures, support endothelial integrity and control vascular permeability. Furthermore, they are able to transmit intracellular signals to coordinate various endothelial biological responses to insure normal vascular function. Immunoglobulin-containing and proline rich receptor-1 (IGPR-1) is a novel cell adhesion molecule that is involved in angiogenesis and in the regulation of endothelial permeability. IGPR-1 is phosphorylated at Ser220, which is required for its ability to mediate actin fibril reorganization. In this study, we demonstrate that the phosphorylation of IGPR-1 at Ser220 is stimulated by cell spreading and cell adhesion in porcine aortic endothelial (PAE) cells. Blocking homophilic trans-dimerization of IGPR-1 by a blocking antibody inhibited cell-density phosphorylation of IGPR-1. More importantly, phosphorylation of IGPR-1 at Ser220 is increased in PAE cells under shear stress, which was essential for IGPR-1-mediated endothelial cell alignment in response to shear stress. Taken together, this study demonstrate that IGPR-1 activity is regulated be endothelial cell spreading and density. And its activity plays an important role in endothelial cell alignment in response to shear stress. / 2020-07-03T00:00:00Z

Thesis (M.S.)--West Virginia University, 2010. / Title from document title page. Document formatted into pages; contains viii, 37 p. : ill. (some col.). Includes abstract. Includes bibliographical references (p. 33-37).

nÃo hà / Com a cirurgia de catarata moderna realizada em cÃrneas normais, independente da tÃcnica cirÃrgica utilizada, hà uma perda celular endotelial mÃdia de 10 a 20%. SubstÃncias viscoelÃsticas foram desenvolvidas com a funÃÃo de manter os espaÃos naturais do olho e conferir proteÃÃo mecÃnica Ãs estruturas intraoculares durante a cirurgia. O objetivo deste estudo foi realizar uma anÃlise comparativa do efeito de duas formulaÃÃes viscoelÃsticas, metilcelulose a 2% e 4%, na proteÃÃo do endotÃlio corneano contra o dano secundÃrio à facoemulsificaÃÃo. Foi realizado um estudo prospectivo, randomizado e duplo cego com pacientes portadores de catarata senil, submetidos à cirurgia de facoemulsificaÃÃo com Implante de Lente Intraocular (LIO). Todos os pacientes foram submetidos a uma avaliaÃÃo oftalmolÃgica completa, incluindo microscopia especular. ApÃs o exame inicial, os pacientes foram randomizados em dois grupos: no grupo A (n=63) foi utilizada a metilcelulose 2% e no grupo B (n=63) a metilcelulose 4%. A mÃdia da Densidade de CÃlulas Endoteliais (DCE) mostrou-se significativamente reduzida (p<0,05), tanto na anÃlise intra como na intergrupo no 1Â, 15 e 30 dias de pÃs-operatÃrio, representando uma perda de cÃlulas endoteliais de 15,26% e 6,79% nos grupos A e B, respectivamente. A Espessura Central da CÃrnea (ECC) mostrou-se aumentada no 1 dia pÃs operatÃrio (DPO) no grupo A, sendo este dado estatisticamente significante (p<0,05). Houve aumento no Coeficiente de VariaÃÃo da tamanho celular (CV) e diminuiÃÃo no Percentual de CÃlulas Hexagonais (6 A), no entanto, sem significÃncia estatÃstica para esses dois parÃmetros. ConcluÃmos que, à despeito das vantagens da metilcelulose a 4% em relaÃÃo à diminuiÃÃo de perdas de cÃlulas endoteliais apÃs facoemulsificaÃÃo, ambos os viscoelÃsticos sÃo semelhantes em relaÃÃo a parÃmetros clÃnicos como ECC, CV e 6A, os quais refletem a manutenÃÃo de condiÃÃes fisiologicamente adequadas para o bom funcionamento do endotÃlio. No entanto, devido à pequena diferenÃa de custo entre os dois produtos e os benefÃcios da metilcelulose 4%, esta pode ser considerada um produto de escolha em cirurgias de catarata de rotina, uma vez que as indicaÃÃes de facoemulsificaÃÃo estÃo sendo cada vez mais precoces, devido Ãs exigÃncias visuais dos pacientes, promovendo, desta forma, cÃrneas mais saudÃveis por longo prazo. / Modern cataract surgery in normal corneas, independent of the surgical technique used, causes a mean 10 to 20% loss of endothelial cells. Viscoelastic substances were developed with the function of maintaining the natural spaces of the eye and providing mechanical protection to the intraocular structures during surgery. The objective of this study was to perform a comparative analysis of the effect of two viscoelastic compositions, methylcellulose 2% and 4%, in corneal endothelial protection against secondary damage to the phacoemulsification procedure. We performed a prospective, randomized, double-blind study with senile cataract patients, submitted to phacoemulsification surgery with intraocular lens (IOL) implant. All patients were submitted to a complete ophthalmological assessment, including specular microscopy. After initial assessment, the patients were randomized into two groups: in Group A (n=63) we used methylcellulose 2%, and in Group B (n=63) methylcellulose 4%. There was no statistically significant difference for the parameters analyzed between groups before surgery. However, at 30 days after surgery, mean density of endothelial cells (DCE) was 2128.78Â277.55 cells/mm in Group A and 2395.79Â262.16 cells/mm in Group B, representing a 15.15 and 6.76% loss of endothelial cells in Groups A and B, respectively. Mean DCE was significantly reduced (p<0.05), in both the inter- and inter-group analysis on the 1st, 15th, and 30th day after surgery. ECC increased on the 1st day after surgery in group A, this datum was statistically significant (p<0.05). There was no statistical difference for the other parameters assessed. In this study, we conclude that, despite the advantages of methylcellulose 4% over 2% in regards to the reduction of endothelial cell loss after phacoemulsification, both viscoelastic substances are similar in relation to clinical parameters such as central corneal thickness, coefficient of variation in cell size and percentage of hexagonal cells, which reflect corneal preservation and maintain adequate physiological conditions for proper endothelial function. However, due to the slight difference in cost between the two products and the benefits of methylcellulose 4% on endothelial cell preservation, this may be considered a choice product in routine cataract surgery, as indications for phacoemulsification are increasingly early, due to patientsâ visual demands, promoting, in this manner, healthier corneas in the long term.

Thesis (Ph. D.)--University of Washington, 2003. / Vita. Includes bibliographical references (leaves 107-130).

The phenomenon known as immunothrombosis has garnered increased attention over the last few years. Much work has been done to characterize the cross talk between hemostasis and the innate immune system. This thesis outlines the role of the vascular endothelial cells during immunothrombotic events as regulators of coagulation, platelet-, and leukocyte recruitment. A newly developed method for investigating the interaction between endothelial cells and the blood compartment illustrated the procoagulant and proinflammatory effects elicited by tumor necrosis factor α activated endothelial cells upon exposure to whole blood. The method was utilized in evaluating treatment of endothelial dysfunction and disruption with a heparin conjugate. Damaged or hypoxic endothelial cells, in addition to basement membrane collagen, that were pretreated with the heparin conjugate prior to contact with blood were found to have reduced activation of coagulation, platelet-, and leukocyte recruitment; in contrast to unfractionated heparin, which had no effect on the aforementioned parameters. The treatment was then investigated in the setting of ischemia reperfusion injury during kidney transplantation and the heparin conjugate was found to bind cultured endothelial cells with high avidity under cold storage conditions. Furthermore, it was found to bind to the renal vasculature during static cold storage and was subsequently found to be beneficial with regard to early graft function in an experimental mouse model of syngeneic kidney transplantation. Recipients of kidneys treated with the heparin conjugate had reduced serum creatinine compared to controls 24 hours after transplantation. Lastly, the anticoagulant properties of the heparin conjugate were investigated in comparison to unfractionated heparin. While the conjugate exerted reduced capacity with regard to thrombin inhibition, it rapidly inhibited the binding of platelets to exposed collagen. The conjugate was furthermore found to preferentially locate to sites of endothelial cell activation at early stage during endotoxic shock in mice. In conclusion, this thesis demonstrates that disrupted functioning of the vascular endothelial cells actively contributes to immunothrombosis, and that it is possible to model endothelial cell function using whole blood assays. Furthermore, this thesis presents a treatment that enhances the hemocompatibility of damaged endothelial cells and subsequently improves the early renal function after kidney transplantation.

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