• BMB Reports
• /
• v.39 no.2
• /
• pp.132-139
• /
• 2006

Vascular endothelial cadherin (VE-cadherin), which belongs to the classical cadherin family, is localized at adherens junctions exclusively in vascular endothelial cells. Biochemical and biomechanical cues regulate the VE-cadherin adhesive potential by triggering the intracellular signals. VE-cadherin-mediated cell adhesion is required for cell survival and endothelial cell deadhesion is required for vascular development. It is therefore crucial to understand how VE-cadherin-based cell adhesion is controlled. This review summarizes the inter-endothelial cell adhesions and introduces our recent advance in Rap1-regulated VE-cadherin adhesion. A further analysis of the VE-cadherin recycling system will aid the understanding of cell adhesion/deadhesion mechanisms mediated by VE-cadherin in response to extracellular stimuli during development and angiogenesis.

• Biomedical Science Letters
• /
• v.12 no.3
• /
• pp.255-259
• /
• 2006

Reactive oxygen species (ROS) is one of the main pathological factors in endothelial disorder. For example, an atherosclerosis is induced by the dysfunction of vascular endothelial cells. The dysfunction of vascular endothelial cells cascades to secrete intercellular adhesion molecule (ICAM)-l substance by ROS. Therefore, The ROS is regraded as an important factor of the injury of vascular endothelial cells and inducement of atherosclerosis. Oxygen radical scavengers playa key role to prevention of many diseases mediated by oxidative stress of ROS. In this study, the toxic effect of ROS on vascular endothelial cells and the effect of antioxidant, vitamin E on bovine pulmonary vascular endothelial cell line (BPVEC) treated with hydrogen peroxide were examined by the colorimetric assay. ROS decreased remarkably cell viability according to the dose- and time-dependent manners. In protective effect of vitamin E on BPVEC treated with hydrogen peroxide, vitamin E increased remarkably cell viability compared with control after BPVEC were treated with $15{\mu}M$ hydrogen peroxide for 6 hours. From these results, it is suggested that ROS has cytotoxicity on cultured BPVEC and oxygen radical scavenger such as vitamin E is very effective in prevention of oxidative stress-induced cytotoxicity.

• Journal of Chest Surgery
• /
• v.26 no.2
• /
• pp.80-85
• /
• 1993

Synthetic and biosynthetic vascular grafts of small diameter have long been considered to be prone to thrombosis, ultimately leading to the complete graft occlusion. Endothelial cell seeding onto synthetic blood-contacting surfaces has been suggested to be an ideal means to solve this problem. This study described a culture method of bovine endothelial cells and evaluated blood-compatibility and seeding efficiency of cultured endothelial cells. Bovine pulmonary artery endothelial cells were harvested enzymatically and grown to confluence on polystyrene culture flask surfaces using established techniques. The identification of endothelial cells was made through the demonstration of expression of factor VIII R:Ag by immunofluorescent technique. To quantitate the effect of improvement in blood-compatibility of viable endothelial cells, endothelial monolayers were exposed to blood containing $\^$111/In-oxine labeled platelets. Viable endothelial monolayers retained less labeled platelets than control surfaces. The Indium-labeled endothelial cells were seeded onto three different blood-contacting surfaces of Dacron vascular graft immobilized in specially equipped wells and incubated for specific time intervals (t=15, 30, 60, 120 minutes). Longer incubation times showed improved cell adherence in collagen-coated and fibrin-coated Dacron vascular graft groups. However in untreated Dacron grafts, no direct relationship was observed between incubation time and endothelial cell seeding efficiency. This may be due to leakage of endothelial cells through porosity of Dacron grafts in this in-vitro experimental condition.

• BMB Reports
• /
• v.48 no.8
• /
• pp.429-430
• /
• 2015

Angiogenesis is a complex process involving dynamic interaction of various cell to cell interactions. Endothelial cell interactions regulated by growth factors, inflammatory cytokines, or hemodynamic stress are critical for balancing vascular quiescence and activation. Yes-associated protein (YAP), an effector of Hippo signaling, is known to play significant roles in maintaining cellular homeostasis. However, its role in endothelial cells for angiogenic regulation remains relatively unexplored. We demonstrated the critical role of YAP in vascular endothelial cells and elucidated the underlying molecular mechanisms involved in angiogenic regulation of YAP. YAP was expressed in active angiogenic regions where endothelial cell junctions were relatively loosened. Consistently, YAP subcellular localization and activity were regulated by VE-cadherin-mediated PI3K/Akt pathway. YAP thereby regulated endothelial sprouting via angiopoietin-2 expression. These results provide an insight into a model of coordinating endothelial junctional stability and angiogenic activation through YAP. [BMB Reports 2015; 48(8): 429-430]

• Biotechnology and Bioprocess Engineering:BBE
• /
• v.5 no.2
• /
• pp.106-109
• /
• 2000

Vascular endothelial cells (EGs) are usually difficult to culture to culture in a large scale because of their complicated requirements for cell growth. As the vascular endothelial growth factor (VEGF) is a key growth factor in the EC culture, we transfected human umbilical vein endothelial cells (HUVEC) using a plasmid containing VEGF gene and let them grow in a culture medium eliminated an important supplement, endothelail cell growth supplement(ECGS). The expression of VEGF by HUVEC tansfected with Vegf GENE was not enough to stimulate the growth of HUVEC, only 40% of maximum cell density obtainable in the presence of ECGS. However, when the culture medium was supplied with 2.5 ng/ml of basic fibroblast growth factor (bFGF), a synergistic effect effect of VEGE and bFGF was observed. In this case, the final cell density was recovered was recovered up to about 78% of maxium value.

• Preventive Nutrition and Food Science
• /
• v.19 no.4
• /
• pp.299-306
• /
• 2014

Hesperetin has been shown to possess a potential anti-angiogenic effect, including vascular formation by endothelial cells. However, the mechanisms underlying the potential anti-angiogenic activity of hesperetin are not fully understood. In the present study, we evaluated whether hesperetin has anti-angiogenic effects in human umbilical vascular endothelial cells (HUVECs). HUVECs were treated with 50 ng/mL vascular endothelial growth factor (VEGF) to induce proliferation as well as vascular formation, followed by treatment with several doses of hesperetin (25, 50, and $100{\mu}M$) for 24 h. Cell proliferation and vascular formation were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tube formation assay, respectively. In addition, cell signaling related to cell proliferation and vascular formation was analyzed by western blot. Furthermore, a mouse aorta ring assay was performed to confirm the effect of hesperetin on vascular formation. Hesperetin treatment did not cause differences in HUVECs proliferation. However, hesperetin significantly inhibited VEGF-induced cell migration and tube formation of HUVECs (P<0.05). Moreover, hesperetin suppressed the expression of ERK, p38 MAPK, and PI3K/AKT in the VEGF-induced HUVECs. In an ex vivo model, hesperetin also suppressed microvessel sprouting of mouse aortic rings. Taken together, the findings suggest that hesperetin inhibited vascular formation by endothelial cells via the inhibition of the PI3K/AKT, ERK and p38 MAPK signaling.

• The Journal of Korean Society of Virology
• /
• v.26 no.1
• /
• pp.47-58
• /
• 1996

Histopathological vascular changes in hemorrhagic fever with renal syndrome (HFRS) caused by Hantaan virus include increased vascular permeability, disseminated intravascular coagulation, thrombocytopenia and changes in coagulation activity. Although vascular endothelial cells of main target organs such as kidney infected with Hantaan virus are not damaged but swelling of endothelial cells, perivascular exudates and infiltration of mononuclear cells and fresh interstitial hemorrhages are common. However, the pathogenesis of cell infiltration and hemorrhages around vascular endothelial cells are not well understood. Some endothelial cell molecules or vascular adhesins that acts as adhesion moleulces for leukocyte are expressed on endothelial cells close to site of inflammation. However, whether the expression of endothelial adhesion molecules such as vascular cell adhesion molecule-1 (VCAM-1), intercellular adhesion molecule (ICAM-1) and endothelial leukocyte adhesion molecule (ELAM) on vascular endothelial cells are increased by infection with Hantaan virus has not been studied. In this study, the relationship between the expression of VCAM-1, ICAM-1 and ELAM and adhesion of mononuclear cells on endothelial cells of human blood vessels infected with Hantaan virus was investigated. The endothelial cells of umbilical vein was passaged three times in culture medium and the monolayered cells were infected with $10^5\;pfu/ml$ of Hantaan virus grown in Vera E6 cell cultures. The multiplication of virus in cultured endothelial cells was monitored by immunohistochemistry and the expression of adhesion molecules was demonstrated by immunohistochemistry using monoclonal antibodies against VCAM-1, ICAM-1 and ELAM. And in situ hybriditation against ICAM-1 was also performed. The endothelial adhesion molecules, VCAM and ICAM, were expressed after 6 hours postinfection, respectively, and their expressions lasted for 72 hours. Similar expression of VCAM and ICAM appeared on endothelial cells by infection with virus, but the expression of ELAM was not recognized up to 72 hours postinfection. Microscopically, it was noted that many monocuclear cells adhered on endothelial cells infected with viruses. In an electronmicroscopic study, the transendothelial migration of mononuclear cells was observed on monolayered endothelial cells infected with virus. This results suggested that the endothelial adhesion molecules, particulary VCAM and ICAM, might be expressed on endothelial cells by infection with Hantaan virus and these molecules play a key role in the adhesion and extravasation of inflammatory cells around blood vessels.

• Preventive Nutrition and Food Science
• /
• v.20 no.4
• /
• pp.221-229
• /
• 2015

Hesperidin has been shown to possess a potential inhibitory effect on vascular formation in endothelial cells. However, the fundamental mechanism for the anti-angiogenic activity of hesperidin is not fully understood. In the present study, we evaluated whether hesperidin has anti-angiogenic effects in mouse embryonic stem cell (mES)-derived endothelial-like cells, and human umbilical vascular endothelial cells (HUVECs), and evaluated their mechanism via the AKT/mammalian target of rapamycin (mTOR) signaling pathway. The endothelial cells were treated with several doses of hesperidin (12.5, 25, 50, and $100{\mu}M$) for 24 h. Cell viability and vascular formation were analyzed using the 3-(4,5-dimethylthiazol-2-yl)-2,5-diphenyltetrazolium bromide and tube formation assay, respectively. Alteration of the AKT/mTOR signaling in vascular formation was analyzed by western blot. In addition, a mouse aortic ring assay was used to determine the effect of hesperidin on vascular formation. There were no differences between the viability of mES-derived endothelial-like cells and HUVECs after hesperidin treatment. However, hesperidin significantly inhibited cell migration and tube formation of HUVECs (P<0.05) and suppressed sprouting of microvessels in the mouse aortic ring assay. Moreover, hesperidin suppressed the expression of AKT and mTOR in HUVECs. Taken together, these findings suggest that hesperidin inhibits vascular formation by blocking the AKT/mTOR signaling pathways.

• BMB Reports
• /
• v.47 no.1
• /
• pp.1-7
• /
• 2014

Atherosclerosis is a pathologic process occurring within the artery, in which many cell types, including T cell, macrophages, endothelial cells, and smooth muscle cells, interact, and cause chronic inflammation, in response to various inner- or outer-cellular stimuli. Atherosclerosis is characterized by a complex interaction of inflammation, lipid deposition, vascular smooth muscle cell proliferation, endothelial dysfunction, and extracellular matrix remodeling, which will result in the formation of an intimal plaque. Although the regulation and function of vascular smooth muscle cells are important in the progression of atherosclerosis, the roles of smooth muscle cells in regulating vascular inflammation are rarely focused upon, compared to those of endothelial cells or inflammatory cells. Therefore, in this review, we will discuss here how smooth muscle cells contribute or regulate the inflammatory reaction in the progression of atherosclerosis, especially in the context of the activation of various membrane receptors, and how they may regulate vascular inflammation.

• Archives of Plastic Surgery
• /
• v.34 no.1
• /
• pp.8-12
• /
• 2007

Purpose: Protein tyrosine kinase(PTK), protein kinase C(PKC), oxidase, as a mediator, have been known to take a role in signal transduction pathway of angiogenesis. The authors confirmed that PKC is the most noticeable mediator for abnormal proliferation of vascular endothelial cells through in vitro study model using the inhibitors, targeting the formation of three co-enzymes. In this study, we would investigate which isoform of PKC play an important role in abnormal angiogenesis of vascular endothelial cell. Methods: In 96 well plates, $10^4$ HUVECs(human umbilical vein endothelial cells) were evenly distributed. Two groups were established; the control group without administration of DMH(1,2-dimethylhydrazine) and the DMH group with administration of $7.5{\times}10^{-9}M$ DMH. RNA was extracted from vascular endothelial cell of each group and expression of the PKC isoform was analyzed by RT-PCR(reverse transcriptase-polymerase chain reaction) method. Results: RT-PCR analysis showed that $PKC{\alpha}$, $-{\beta}I$, $-{\beta}II$, $-{\eta}$, $-{\mu}$ and $-{\iota}$ were expressed in vascular endothelial cells of each group. DMH incresed the expression of $PKC{\alpha}$ and $PKC{\mu}$, and decreased $PKC{\beta}I$, $PKC{\beta}II$ expression dominantly. Conclusion: Based on the result of this study, it was suggested that $PKC{\alpha}$ and $PKC{\mu}$ may have significant role in abnormal proliferation of vascular endothelial cell.