• Maxillofacial Plastic and Reconstructive Surgery
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• v.36 no.3
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• pp.85-93
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• 2014

Purpose: Nodal metastasis is the main prognostic factor in the patients with oral squamous cell carcinoma (OSCC). We investigated the association between tumor-associated lymphatics and OSCC characteristics. Methods: Thirty-four specimens were used for the immunohistochemical staining with the antibody for vascular endothelial growth factor (VEGF)-C, VEGF-D, VEGF receptor (VEGFR)-3, phosphorylated VEGFR-3, D2-40, and matrix metallproteinases (MMPs). We observed the distribution of the lymphangiogenic factors and quantified the degree of expression. We determined lymphatic vessel density (LVD) and lymphatic vessel dilatation with D2-40 immunostaining. We assessed the association of LVD or lymphatic vessel dilatation with tumor progression or tumor differentiation. Results: OSCC cells expressed lymphangiogenic ligands. Lymphangiogenic receptor, VEGFR-3, was expressed and activated in some tumor cells as well as in tumor-associated endothelial cells. LVD was not associated with tumor size or nodal status, but lymphatic vessel dilatation was higher in tumors with nodal metastasis, and also higher in poorly differentiated tumors. In stromal area of OSCC, MMP-1 and MMP-10 were up-regulated and the basement membrane of tumor-associated endothelial cells was destroyed by these collagenases. Conclusion: In the primary tumors with nodal metastasis, especially in poorly differentiated OSCC, tumor cells invaded the dilated lymphatic vessels via ruptured sites. MMP-1 and MMP-10 are important in the lysis of the glycocalyx inside the tumor-associated lymphatic endothelial cells.

• Journal of Biomedical Engineering Research
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• v.16 no.4
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• pp.463-470
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• 1995

Complete prelining of artificial vascular grafts with autologous endothelial cells may be one of the ideal solutions to obtain a nonthrombogenlc blood-contacting surface. To establish an intact endothelial cell monolayer on a prosthetic surface at the time of implantation,a sufficient number of endothelial cells and adequate propagation condition In cell culture are prerequisites. In this experimental study, endothelial cells from microvessels of adult human oriental adipose tissue were enzymatically harvested, and optimal culture conditions for proliferation of the endothelial cells in cell culture were examined. Human oriental adipose tissue was digested with collagenase and endothelial cells were separated from other stromal elements by mesh filtration method. Cultured cells were identified as endothelial cells by immunofluorescent staining for factor VIII-related antigen. Proliferation in usual 20% fetal bovine serum (FBS) medium or medium containing endothelial cell growth factor (ECGF)(5 ng/ml) and heparin (HEP)(1,000 units/ml) were compared,and the effects of adding compounds that increase intracellular cyclic adenosine monophosphate levels, that is,cholera toxin (CT)(1 $\mu\textrm{g}$/ml) and isobutylmethylxanthine (IBMX)(0.2 ml),were also analyzed. In total,following eight media groups were examined. 1) FBS medium + ECGF + HEP, 2) FBS medium + ECGF + HEP+CT, 3) FBS medium+ECGF+HEP+lBMX, 4) FBS medium+ECGF+HEP+CT+ IBMX, 5) FBSmedium, 6) FBS medium +CT, 7) FBS medium + IBMX, 8) FBS medium + CT + IBMX. It was shown that the medium containing ECGF + HEP with or without cholera toxin was most efficient in Stimulating cell proliferation. IBMX was considered to have antagonistic effect to ECGF. Among experimental groups without ECGF and HEP, the addition of cholera toxin and IBMX was shown to significantly potentiate cell proliferation. This results could provide a practical method for use of cultured human endothelial cells for endothelial cell seeding of cardiovascular prosthetic device, particularly in small-diameter vascular grafts.

• Journal of Yeungnam Medical Science
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• v.7 no.2
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• pp.27-37
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• 1990

To investigate the changing patterns of microfilament and microtubule arrangement and influence of myocardial cells and colchicine to microfilament and microtubule formation in cardiac endothelial cells the authors carried out indirect immunofluorescence stain for actin and tubulin with supernatant monoclonal antibodies. Secondary antibodies were IgG FITC conjugate. The results were summerized as follows. Fiberform reactions were stronger in the cells with many processes and spread cytoplasm and they became weaker after the endothelial cells formed monolayer. In the endothelial cells cocultured with myocardial cells the fiberform of the microtubule became less visible compared to control group but fiberform of the microtubule maintained strong intensity as endothelial cells formed monolayer. In the group treated with colchicine, there were no visible differences in microfilaments compared to control group but fiberform of microtubule revealed weaker intensity after colchicine treatment. The intensity of microtubule fiberform returned to control level after 2 days.

• Biomolecules & Therapeutics
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• v.26 no.2
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• pp.93-100
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• 2018

Carbon monoxide (CO) is a gaseous molecule produced from heme by heme oxygenase (HO). Endogenous CO production occurring at low concentrations is thought to have several useful biological roles. In mammals, especially humans, a proper neurovascular unit comprising endothelial cells, pericytes, astrocytes, microglia, and neurons is essential for the homeostasis and survival of the central nervous system (CNS). In addition, the regeneration of neurovascular systems from neural stem cells and endothelial precursor cells after CNS diseases is responsible for functional repair. This review focused on the possible role of CO/HO in the neurovascular unit in terms of neurogenesis, angiogenesis, and synaptic plasticity, ultimately leading to behavioral changes in CNS diseases. CO/HO may also enhance cellular networks among endothelial cells, pericytes, astrocytes, and neural stem cells. This review highlights the therapeutic effects of CO/HO on CNS diseases involved in neurogenesis, synaptic plasticity, and angiogenesis. Moreover, the cellular mechanisms and interactions by which CO/HO are exploited for disease prevention and their therapeutic applications in traumatic brain injury, Alzheimer's disease, and stroke are also discussed.

• Maxillofacial Plastic and Reconstructive Surgery
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• v.32 no.6
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• pp.504-510
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• 2010

Purpose: This study was to examine the proliferation and function of the adipose tissue-derived endothelial cells according to different culture medium conditions. Materials and Methods: Adipose tissue-derived CD146 positive endothelial cells were cultured in according to different culture mediums (DMEM culture medium with or without osteogenic inductive agents and EBM-2 culture medium with or without osteogenic inductive agents). The proliferation and function of the adipose tissue-derived endothelial cells was examined in different culture medium conditions. Results: Adipose tissue-derived endothelial cells formed tube-like structures on Matrigel in EBM-2 culture medium with or without osteogenic inductive agents. However, the cells did not form tube-like structures on Matrigel in DMEM medium with or without osteogenic inductive agents. After 24 hours of culture, among the culture medium using EBM-2, the proliferation of the cells were promoted in EBM-2 medium without osteogenic inductive agents than in EBM-2 medium with osteogenic inductive agents. However, 72 hours of culture, the proliferation of the cells were promoted in EBM-2 medium with osteogenic inductive agents than in EBM-2 medium without osteogenic inductive agents. Conclusion: These results suggest that the proliferation and function of the adipose tissue-derived CD146 positive endothelial cells could be maintained in EBM-2 with osteogenic inductive agents.

• BMB Reports
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• v.42 no.10
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• pp.685-690
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• 2009

Angiogenesis is essential for tumor growth and vascular endothelial cell growth factor (VEGF) plays a key role in this process. Conversely, sphingosine 1-phosphate (S1P) is a biologically active sphingolipid known to play a key role in cancer progression by regulating endothelial cell proliferation and migration. In this study, the authors found that S1P increases the level of VEGF mRNA in human umbilical vein endothelial cells (HUVECs) and immortalized HUVECs (iHUVECs). Additionally, S1P was found to increase VEGF promoter activity in MS-1 mouse pancreatic islet endothelial cells. Furthermore, a pharmacological inhibitory study revealed that $G_{\alpha i/o}$-mediated phospholipase C, Akt, Erk, and p38 MAPK signaling are involved in this S1P-induced expression of VEGF. A component of AP1 transcription factor is important for S1P-induced VEGF expression. Taken together, these findings suggest that S1P enhances endothelial cell proliferation and migrat ion by upregulating the expression of VEGF mRNA.

• Nutritional Sciences
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• v.9 no.1
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• pp.3-8
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• 2006

Functional damage to microvascular endothelial cells by hyperglycemia is thought to be one of the critical risk factor.; in the impaired wound healing seen with diabetes mellitus. It is also thought that oxidative stress plays a significant role in this endothelial cell dysfunction. The present study examined the differential effects of flavonoids on endothelial cell dysfunction under high glucose conditions. Human endothelial cells exposed to 30 mmol/L glucose for 7 d were pre-treated with various flavonoids and pulse-treated with 0.2 mmol/L $H_2O_2$ for 30 min. High glucose markedly decreased cell viability with elevated oxidant generation and nuclear condensation. $H_2O_2$ insult exacerbated endothelial cytotoxicity due to chronic exposure to high glucose. (-)Epigallocatechin gallate and quercetin improved glucose-induced cell damage with the disappearnnce of apoptotic bodies, whereas apigenin intensified the glucose cytotoxicity. In addition, cell viability data revealed that these flavonoids of (-)epigallocatechin gallate and quercetin substantially attenuated both high glucose- and $H_2O_2$- induced dual endothelial damage. These results suggest that (-)epigallocatechin gallate and quercetin may be beneficial agents for improving endothelial cell dysfunction induced by high glucose and may prevent or reduce the development of diabetic vascular complications.

• BMB Reports
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• v.39 no.4
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• pp.339-345
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• 2006

The blood-neural barrier (BNB), including blood-brain barrier (BBB) and blood-retinal barrier (BRB), is an endothelial barrier constructed by an extensive network of endothelial cells, astrocytes and neurons to form functional 'neurovascular units', which has an important role in maintaining a precisely regulated microenvironment for reliable neuronal activity. Although failure of the BNB may be a precipitating event or a consequence, the breakdown of BNB is closely related with the development and progression of CNS diseases. Therefore, BNB is most essential in the regulation of microenvironment of the CNS. The BNB is a selective diffusion barrier characterized by tight junctions between endothelial cells, lack of fenestrations, and specific BNB transporters. The BNB have been shown to be astrocyte dependent, for it is formed by the CNS capillary endothelial cells, surrounded by astrocytic end-foot processes. Given the anatomical associations with endothelial cells, it could be supposed that astrocytes play a role in the development, maintenance, and breakdown of the BNB. Therefore, astrocytes-endothelial cells interaction influences the BNB in both physiological and pathological conditions. If we better understand mutual interactions between astrocytes and endothelial cells, in the near future, we could provide a critical solution to the BNB problems and create new opportunities for future success of treating CNS diseases. Here, we focused astrocyte-endothelial cell interaction in the formation and function of the BNB.

• The Journal of Korean Society for Radiation Therapy
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• v.14 no.1
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• pp.165-174
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• 2002

Vascular endothelial growth factor (VEGF) has been identified as a peptide growth factor specific for vascular endothelial cells. In this study, we examined the effect of VEGF on radiation induced apoptosis and receptor/second messenger signal transduction pathway for VEGF effect in human umbilical vein endothelial cells (HUVECs). VEGF was found to protect HUVECs against the lethal effects of ionizing radiation by inhibiting the apoptosis induced in these cells by radiation exposure. VEGF (1-30 ng/ml) dose dependently inhibited apoptosis by irradiation. Pre-treatment with Flt-1 and Flk-l/KDR receptor blocked the VEGF-in duced antiapoptotic effect. Phosphatidylinositol 3'-kinase (PI3-kinase) specific inhibitor, Wortman in and LY294002, blocked the VEGF-induced antiapoptotic effect. These data suggest that VEGF may play an important role in survival of HUVECs due to the prevention of apoptotic cell death caused by some stresses such as ionizing radiation.

• The Korean Journal of Physiology and Pharmacology
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• v.25 no.5
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• pp.425-437
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• 2021

Although the contributions of sitagliptin to endothelial dysfunction in diabetes mellitus were previously reported, the mechanisms still undefined. Autophagy plays an important role in the development of diabetes mellitus, but its role in diabetic macrovascular complications is unclear. This study aims to observe the effect of sitagliptin on macrovascular endothelium in diabetes and explore the role of autophagy in this process. Diabetic rats were induced through administration of high-fat diet and intraperitoneal injection of streptozotocin. Then diabetic rats were treated with or without sitagliptin for 12 weeks. Endothelial damage and autophagy were measured. Human umbilical vein endothelial cells were cultured either in normal glucose or in high glucose medium and intervened with different concentrations of sitagliptin. Rapamycin was used to induce autophagy. Cell viability, apoptosis and autophagy were detected. The expressions of proteins in c-Jun N-terminal kinase (JNK)-Bcl-2-Beclin-1 pathway were measured. Sitagliptin attenuated injuries of endothelium in vivo and in vitro. The expression of microtubuleassociated protein 1 light chain 3 II (LC3II) and beclin-1 were increased in aortas of diabetic rats and cells cultured with high-glucose, while sitagliptin inhibited the over-expression of LC3II and beclin-1. In vitro pre-treatment with sitagliptin decreased rapamycin-induced autophagy. However, after pretreatment with rapamycin, the protective effect of sitagliptin on endothelial cells was abolished. Further studies revealed sitagliptin increased the expression of Bcl-2, while inhibited the expression of JNK in vivo. Sitagliptin attenuates injuries of vascular endothelial cells caused by high glucose through inhibiting over-activated autophagy. JNK-Bcl-2-Beclin-1 pathway may be involved in this process.