• Advances in nano research
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• v.12 no.5
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• pp.501-514
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• 2022

This study aimed to investigate the effects and potential mechanisms of Chikusetsusaponin V (CsV) on endothelial nitric oxide synthase (eNOS) and vascular endothelial cell functions. Different concentrations of CsV were added to animal models, bovine aorta endothelial cells (BAECs) and human umbilical vein endothelial cells (HUVECs) cultured in vitro. qPCR, Western blotting (WB), and B ultrasound were performed to explore the effects of CsV on mouse endothelial cell functions, vascular stiffness and cellular eNOS mRNA, protein expression and NO release. Bioinformatics analysis, network pharmacology, molecular docking and protein mass spectrometry analysis were conducted to jointly predict the upstream transcription factors of eNOS. Furthermore, pulldown and ChIP and dual luciferase assays were employed for subsequent verification. At the presence or absence of CsV stimulation, either overexpression or knockdown of purine rich element binding protein A (PURA) was conducted, and PCR assay was employed to detect PURA and eNOS mRNA expressions, Western blot was used to detect PURA and eNOS protein expressions, cell NO release and serum NO levels. Tube formation experiment was conducted to detect the tube forming capability of HUVECs cells. The animal vasodilation function test detected the vasodilation functions. Ultrasonic detection was performed to determine the mouse aortic arch pulse wave velocity to identify aortic stiffness. CsV stimulus on bovine aortic cells revealed that CsV could upregulate eNOS protein levels in vascular endothelial cells in a concentration and time dependent manner. The expression levels of eNOS mRNA and phosphorylation sites Ser1177, Ser633 and Thr495 increased significantly after CsV stimulation. Meanwhile, CsV could also enhance the tube forming capability of HUVECs cells. Following the mice were gavaged using CsV, the eNOS protein level of mouse aortic endothelial cells was upregulated in a concentration- and time-dependent manner, and serum NO release and vasodilation ability were simultaneously elevated whereas arterial stiffness was alleviated. The pulldown, ChIP and dual luciferase assays demonstrated that PURA could bind to the eNOS promoter and facilitate the transcription of eNOS. Under the conditions of presence or absence of CsV stimulation, overexpression or knockdown of PURA indicated that the effect of CsV on vascular endothelial function and eNOS was weakened following PURA gene silence, whereas overexpression of PURA gene could enhance the effect of CsV upregulating eNOS expression. CsV could promote NO release from endothelial cells by upregulating the expression of PURA/eNOS pathway, improve endothelial cell functions, enhance vasodilation capability, and alleviate vessel stiffness. The present study plays a role in offering a theoretical basis for the development and application of CsV in vascular function improvement, and it also provides a more comprehensive understanding of the pharmacodynamics of CsV.

• Journal of information and communication convergence engineering
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• v.5 no.2
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• pp.155-158
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• 2007

An area distribution of Corneal Endothelial Cell(CEC) include important clinical information. In this paper, we present a two-step processing method of contour complement for the CEC. In the first step; we apply not only conventional Laplasian Gaussian filters(LGF) but also three-arrow-shaped LGFs which is newly developed to extract vertices of hexagonal shapes. In the second step; we complement the lacking part of CEC by using an energy minimum algorithm. Using the results, we measure areas of CEC.

• The Korean Journal of Physiology and Pharmacology
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• v.20 no.5
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• pp.533-538
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• 2016

Angiogenesis plays an essential role in embryo development, tissue repair, inflammatory diseases, and tumor growth. In the present study, we showed that endothelial nitric oxide synthase (eNOS) regulates retinal angiogenesis. Mice that lack eNOS showed growth retardation, and retinal vessel development was significantly delayed. In addition, the number of tip cells and filopodia length were significantly reduced in mice lacking eNOS. Retinal endothelial cell proliferation was significantly blocked in mice lacking eNOS, and EMG-2-induced endothelial cell sprouting was significantly reduced in aortic vessels isolated from eNOS-deficient mice. Finally, pericyte recruitment to endothelial cells and vascular smooth muscle cell coverage to blood vessels were attenuated in mice lacking eNOS. Taken together, we suggest that the endothelial cell function and blood vessel maturation are regulated by eNOS during retinal angiogenesis.

• BMB Reports
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• v.52 no.2
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• pp.111-112
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• 2019

Although many studies have reported that the breakdown of the blood-brain barrier (BBB) represents one of the major pathological changes in aging, the mechanism underlying this process remains relatively unexplored. In this study, we described that acid sphingomyelinase (ASM) derived from endothelial cells plays a critical role in BBB disruption in aging. ASM levels were elevated in the brain endothelium and plasma of aged humans and mice, resulting in BBB leakage through an increase in caveolae-mediated transcytosis. Moreover, ASM caused damage to the caveolae-cytoskeleton via protein phosphatase 1-mediated ezrin/radixin/moesin dephosphorylation in primary mouse brain endothelial cells. Mice overexpressing brain endothelial cell-specific ASM exhibited acceleration of BBB impairment and neuronal dysfunction. However, genetic inhibition and endothelial specific knock-down of ASM in mice improved BBB disruption and neurocognitive impairment during aging. Results of this study revealed a novel role of ASM in the regulation of BBB integrity and neuronal function in aging, thus highlighting the potential of ASM as a new therapeutic target for anti-aging.

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

• Journal of Biomedical Engineering Research
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• v.17 no.2
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• pp.255-262
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• 1996

Antithrombogenic surFace is one of the most important things to the artificial vascular prostheses. This problem will be solved if the surface of prosthesis is covered with endothelial cells. The attachment and the growth of endothelial cells onto vascular prosthesis are very difficult. So many studies have been concentrated on the attachement of endothelial cell. But no good performance of the in uiwo experiments has been shown until now. In this study, we used the whole extracellular matrix (ECM) excreted from fibroblasts as an underlying matrix, and the endothelial cells were seeded to obtain the long term patency of vascular graft(i.e., for the patent 8 week implanted wafts in the animal model of rat). In order to study the antithrombogenic functions of cultured endothelial cells, prostaglandin(PGF 1 a) synthesis and platelet adhesion were assayed. The concentration of PGF a of stimulated group was sisnificantly higher than that of control group(21.97 $\pm$ 3.45 vs 4.93 $\pm$0.71 pg/1000 cells). The platelet adhesion of the polyurethane sheet covered with endothelial cells was lower than that of polyurethane sheet or sheet covered with ECM(1.04$\pm$0.28, 2.87$\pm$0.77, 2.89$\pm$0.70, % radioactivities, respectively). Endothelial cells grew well on polyurethane coated with ECM, synthesized the prostacyclin and functioned well as antithrombogenic. Therefore the endothelialization onto the ECM excreted from fibroblasts may be a good method for the vfudig prosthesis.

• Biomedical Science Letters
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• v.11 no.1
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• pp.79-84
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• 2005

This study was performed to determine whether postprandial hypertriglyceridemia can affect the endothelial function. Endothelial function was assessed by flow-mediated endothelium-dependent brachial artery vasodilation (FMD) which was defined as percentile changes of diameter. Thirty one patients were enrolled in this study. The serum lipid profiles and FMD were measured at fasting, and after low fat and high fat meals. The serum triglycerides at 2 hours after a high fat meal were significantly increased compared to those measured at 2 hours after a low-fat meal and at fasting state (P<0.05). The FMD was transiently decreased (P<0.0001) from $11.4{\pm}3.2\%$ at fasting state to $6.5{\pm}2.5\%$ after a high-fat meal. The FMD was inversely related with postprandial hypertriglyceridemia (P<0.05). In conclusion, this study may suggest that postprandial hypertriglyceridemia causes endothelial dysfunction.

• Molecules and Cells
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• v.38 no.12
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• pp.1029-1036
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• 2015

Appropriate vessel development and its coordinated function is essential for proper embryogenesis and homeostasis in the adult. Defects in vessels cause birth defects and are an important etiology of diseases such as cardiovascular disease, tumor and diabetes retinopathy. The accumulative data indicate that ETV2, an ETS transcription factor, performs a potent and indispensable function in mediating vessel development. This review discusses the recent progress of the study of ETV2 with special focus on its regulatory mechanisms and cell fate determining role in developing mouse embryos as well as somatic cells.

• Journal of Life Science
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• v.30 no.7
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• pp.651-659
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• 2020

Cardiovascular disease is one of the leading causes of death across the world, and gold-standard treatments such as percutaneous coronary intervention and artery bypass grafting have various limitations including myocardial damage and subsequent maladaptive cardiac remodeling. To overcome this, stem-cell therapies are emerging as a promising strategy for cardiovascular regeneration. Endothelial progenitor cells (EPCs) have high potential to proliferate and differentiate into endothelial cells for vascularization and tissue regeneration, and several clinical trials have explored EPC function in tissue repair in relation to clinical safety and improving cardiac function. Consequently, EPC has been suggested as a feasible stem-cell therapy. However, autologous EPC transplantation in cardiovascular disease patients is restricted by risk factors such as age, smoking status, and hypertension that lead to reduced bioactivity in the EPCs. New approaches for improving EPC function and stem-cell efficacy have therefore been suggested, including cell priming, organoid culture systems, and enhancing transplantation efficiency through 3D bioprinting methods. In this review, we provide a comprehensive understanding of EPC characteristics, therapeutic approaches, and the current state of clinical research into EPCs as stem-cell therapy for cardiovascular disease.

• Journal of Nutrition and Health
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• v.31 no.8
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• pp.1235-1243
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• 1998

Although an elevated plasma level of high density lipoprotein (HDL) is known as a protective component against the development of atherosclerosis and ensuing coronary heart diseases, the related mechanisms are still not established . It has been clearly demonstrated in the early stages of atherogenesis that adhesion of monocytes and lymphocytes to the vascular endothelium is enhanced via adhesion molecules, and that monocytes and macrophages accumulate in the subendothelial space. The present study has investigated whether isolated plasma HDL plays a role in protection against atherogenesis by inhibiting the expression of vascular cell adhesioin molecule-1(VCAM-1) on the endothelial cells. Effects of plasma native low density lipoprotein (LDL) and ac ethylated LDL(AcLDL) on VCAM-1 expression were also examined by using an immunocytochemical technique. While plasma HDL did not alter the basal expression of VCAM-1 , lipopolysaccharide(LPS) induction of this adhesion modlecule was markedly inhibited at a phyaiological concentration of HDL. In contrast, 30$\mu\textrm{g}$ protein/ml AcLDL increased sifnificantly both basal VCAM-1 expression and its LPD induction , suggesting that this modified LDL enhances leukocyte adhesiion to endothelial cells. Unlike AcLDL , plasma native LDL inhibited significantly VCAM-1 expression. This indicates that LDL did not undergo oxidative modificantion while incubated with endothelial cells. These results suggest that plasam HDL may inhibit atherogenesis by reducing the expression of adhesion molecules, which is a protective mechanism independent of tis reverse cholesterol transport function . Modified LDL is a potent iducer for adhesion molecules in vascular endothelical cells and could play a role in the pathogenesis of atherosclerosis by adhering to blood cells.