• Title, Summary, Keyword: vascular formation

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Hesperetin Inhibits Vascular Formation by Suppressing of the PI3K/AKT, ERK, and p38 MAPK Signaling Pathways

  • Kim, Gi Dae
    • Preventive Nutrition and Food Science
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    • v.19 no.4
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    • pp.299-306
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    • 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.

Hesperidin Inhibits Vascular Formation by Blocking the AKT/mTOR Signaling Pathways

  • Kim, Gi Dae
    • Preventive Nutrition and Food Science
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    • v.20 no.4
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    • pp.221-229
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    • 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.

Extravasating Neutrophil-derived Microparticles Preserve Vascular Barrier Function in Inflamed Tissue

  • Lim, Kihong;Sumagin, Ronen;Hyun, Young-Min
    • IMMUNE NETWORK
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    • v.13 no.3
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    • pp.102-106
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    • 2013
  • Emerging evidence suggests that gap formation and opening of the endothelial junctions during leukocyte extravasation is actively controlled to maintain the integrity of the vascular barrier. While the role for endothelial cells to this process has been well defined, it is not clear whether leukocytes are also actively contributing to endothelial barrier function. We have recently showed that extravasating leukocytes deposit microparticles on the subendothelium during the late stages of extravasation, which is LFA-1 dependent. Using multiphotonintravital microscopy (MP-IVM) of mouse cremaster muscle vessels in the current work, we show that microparticle formation and deposition maintains the integrity of the microvascular barrier during leukocyte extravasation. Inhibition of neutrophil-derived microparticle formation resulted in dramatically increased vascular leakage. These findings suggest that deposition of microparticles during neutrophil extravasation is essential for maintaining endothelial barrier function and may result in temporal difference between neutrophil extravasation and an increase in vascular leakage.

New Aspects of Vascular Calcification: Histone Deacetylases and Beyond

  • Kwon, Duk-Hwa;Kim, Young-Kook;Kook, Hyun
    • Journal of Korean Medical Science
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    • v.32 no.11
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    • pp.1738-1748
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    • 2017
  • Vascular calcification is a pathologic phenomenon in which calcium phosphate is ectopically deposited in the arteries. Previously, calcification was considered to be a passive process in response to metabolic diseases, vascular or valvular diseases, or even aging. However, now calcification is recognized as a highly-regulated consequence, like bone formation, and many clinical trials have been carried out to elucidate the correlation between vascular calcification and cardiovascular events and mortality. As a result, vascular calcification has been implicated as an independent risk factor in cardiovascular diseases. Many molecules are now known to be actively associated with this process. Recently, our laboratory found that posttranslational modification of histone deacetylase (HDAC) 1 is actively involved in the development of vascular calcification. In addition, we found that modulation of the activity of HDAC as well as its protein stability by MDM2, an HDAC1-E3 ligase, may be a therapeutic target in vascular calcification. In the present review, we overview the pathomechanism of vascular calcification and the involvement of posttranslational modification of epigenetic regulators.

Two-Cell Spheroid Angiogenesis Assay System Using Both Endothelial Colony Forming Cells and Mesenchymal Stem Cells

  • Shah, Sajita;Kang, Kyu-Tae
    • Biomolecules & Therapeutics
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    • v.26 no.5
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    • pp.474-480
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    • 2018
  • Most angiogenesis assays are performed using endothelial cells. However, blood vessels are composed of two cell types: endothelial cells and pericytes. Thus, co-culture of two vascular cells should be employed to evaluate angiogenic properties. Here, we developed an in vitro 3-dimensional angiogenesis assay system using spheroids formed by two human vascular precursors: endothelial colony forming cells (ECFCs) and mesenchymal stem cells (MSCs). ECFCs, MSCs, or ECFCs+MSCs were cultured to form spheroids. Sprout formation from each spheroid was observed for 24 h by real-time cell recorder. Sprout number and length were higher in ECFC+MSC spheroids than ECFC-only spheroids. No sprouts were observed in MSC-only spheroids. Sprout formation by ECFC spheroids was increased by treatment with vascular endothelial growth factor (VEGF) or combination of VEGF and fibroblast growth factor-2 (FGF-2). Interestingly, there was no further increase in sprout formation by ECFC+MSC spheroids in response to VEGF or VEGF+FGF-2, suggesting that MSCs stimulate sprout formation by ECFCs. Immuno-fluorescent labeling technique revealed that MSCs surrounded ECFC-mediated sprout structures. We tested vatalanib, VEGF inhibitor, using ECFC and ECFC+MSC spheroids. Vatalanib significantly inhibited sprout formation in both spheroids. Of note, the $IC_{50}$ of vatalanib in ECFC+MSC spheroids at 24 h was $4.0{\pm}0.40{\mu}M$, which are more correlated with the data of previous animal studies when compared with ECFC spheroids ($0.2{\pm}0.03{\mu}M$). These results suggest that ECFC+MSC spheroids generate physiologically relevant sprout structures composed of two types of vascular cells, and will be an effective pre-clinical in vitro assay model to evaluate pro- or anti-angiogenic property.

Cervical Radiculopathy Caused by Vertebral Artery Loop Formation : A Case Report and Review of the Literature

  • Kim, Hoon-Soo;Lee, June-Ho;Cheh, Gene;Lee, Sang-Ho
    • Journal of Korean Neurosurgical Society
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    • v.48 no.5
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    • pp.465-468
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    • 2010
  • Vertebral artery loop formation causing encroachment on cervical neural foramen and canal is a rare cause of cervical radiculopathy. We report a case of 61-year-old woman with vertebral artery loop formation who presented with right shoulder pain radiating to her arm for 2 years. Plain radiograph and computed tomography scan revealed widening of the right intervertebral foramen at the C5-6 level. Magnetic resonance imaging and angiogram confirmed the vertebral artery loop formation compressing the right C6 nerve root. We had considered microdecompressive surgery, but the patient's symptoms resolved after conservative management. Clinician should keep in mind that vertebral artery loop formation is one of important causes of cervical radiculopathy. Vertebral artery should be visualized using magnetic resonance angiography in suspected case.

Hypoxia-dependent mitochondrial fission regulates endothelial progenitor cell migration, invasion, and tube formation

  • Kim, Da Yeon;Jung, Seok Yun;Kim, Yeon Ju;Kang, Songhwa;Park, Ji Hye;Ji, Seung Taek;Jang, Woong Bi;Lamichane, Shreekrishna;Lamichane, Babita Dahal;Chae, Young Chan;Lee, Dongjun;Chung, Joo Seop;Kwon, Sang-Mo
    • The Korean Journal of Physiology and Pharmacology
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    • v.22 no.2
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    • pp.203-213
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    • 2018
  • Tumor undergo uncontrolled, excessive proliferation leads to hypoxic microenvironment. To fulfill their demand for nutrient, and oxygen, tumor angiogenesis is required. Endothelial progenitor cells (EPCs) have been known to the main source of angiogenesis because of their potential to differentiation into endothelial cells. Therefore, understanding the mechanism of EPC-mediated angiogenesis in hypoxia is critical for development of cancer therapy. Recently, mitochondrial dynamics has emerged as a critical mechanism for cellular function and differentiation under hypoxic conditions. However, the role of mitochondrial dynamics in hypoxia-induced angiogenesis remains to be elucidated. In this study, we demonstrated that hypoxia-induced mitochondrial fission accelerates EPCs bioactivities. We first investigated the effect of hypoxia on EPC-mediated angiogenesis. Cell migration, invasion, and tube formation was significantly increased under hypoxic conditions; expression of EPC surface markers was unchanged. And mitochondrial fission was induced by hypoxia time-dependent manner. We found that hypoxia-induced mitochondrial fission was triggered by dynamin-related protein Drp1, specifically, phosphorylated DRP1 at Ser637, a suppression marker for mitochondrial fission, was impaired in hypoxia time-dependent manner. To confirm the role of DRP1 in EPC-mediated angiogenesis, we analyzed cell bioactivities using Mdivi-1, a selective DRP1 inhibitor, and DRP1 siRNA. DRP1 silencing or Mdivi-1 treatment dramatically reduced cell migration, invasion, and tube formation in EPCs, but the expression of EPC surface markers was unchanged. In conclusion, we uncovered a novel role of mitochondrial fission in hypoxia-induced angiogenesis. Therefore, we suggest that specific modulation of DRP1-mediated mitochondrial dynamics may be a potential therapeutic strategy in EPC-mediated tumor angiogenesis.

Role of vascular smooth muscle cell in the inflammation of atherosclerosis

  • Lim, Soyeon;Park, Sungha
    • 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.

Baicalin, baicalein and wogonin inhibits high glucose-induced vascular inflammation in vitro and in vivo

  • Ku, Sae-Kwang;Bae, Jong-Sup
    • BMB Reports
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    • v.48 no.9
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    • pp.519-524
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    • 2015
  • Vascular inflammatory process has been suggested to play a key role in initiation and progression of atherosclerosis, a major complication of diabetes mellitus. Thus, in this study, we attempted to determine whether three structurally related polyphenols found in the Chinese herb Huang Qui, namely baicalin, baicalein, and wogonin, can suppress vascular inflammatory processes induced by high glucose (HG) in human umbilical vein endothelial cells (HUVECs) and mice. Data showed that HG induced markedly increased vascular permeability, monocyte adhesion, expressions of cell adhesion molecules (CAMs), formation of reactive oxygen species (ROS) and activation of nuclear factor (NF)-κB. Remarkably, all of the above mentioned vascular inflammatory effects of HG were attenuated by pretreatment with baicalin, baicalein, and wogonin. Vascular inflammatory responses induced by HG are critical events underlying development of various diabetic complications, therefore, our results suggest that baicalin, baicalein, and wogonin may have significant therapeutic benefits against diabetic complications and atherosclerosis. [BMB Reports 2015; 48(9): 519-524]