• 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.

• 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.

• 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.

• 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.

• 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.

• Fisheries and Aquatic Sciences
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• v.25 no.10
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• pp.517-524
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• 2022

Over production of methylglyoxal (MGO) a highly reactive dicarbonyl compound, has been associated in progressive diabetes with vascular complication. Therefore, we investigated whether hot water extract of Loliolus beka meat (LBM-HWE) presents a preserve effect against MGO-induced cellular damage in human umbilical vein endothelial cells (HUVECs). The LBM-HWE extract showed to inhibit MGO-induced cytotoxicity. Additionally, the LBM-HWE reduced mRNA expression of pro-inflammatory cytokines, and reduced MGO-induced advanced glycation end product (AGEs) formation. Furthermore, LBM-HWE induced glyoxalase-1 mRNA expression and reduced MGO-induced carbonyl protein formation in HUVECs. The results implicate that LBM-HWE has protective ability against MGO-induced HUVECs toxicity by preventing AGEs formation. In conclusion, LBM-HWE could be used as a potential treatment material for the prevention of vascular complications of diabetes.

• Biomolecules & Therapeutics
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• v.6 no.3
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• pp.269-275
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• 1998

These studies were conducted to investigate the antiinflammatory effects and the mechanism of action of natural products. We used the methods of "carrageenan induced foot edema" , "PAF (platelet activating factor) induced foot edema" , "inhibition test of vascular permeability" , "inhibition test of white blood cell migration" , "formation of granuloma" and "adjuvant induced arthritis" to examine the antiinflammatory erects of Angelica gigas, Ledebouriella seseloides, Ginkgo biloba and Bamboo salt (Jukyom). The oral administration of the water extract of Angelica gigantis radix, the methanolic extract of Ginkgo folium and the aqueous solution of Bamboo salt showed antiinflammatory effect on carrageenan and PAF induced foot edema in SD rat at a dose of 1 g/kg. The same administration of methanolic extract of Ginkgo folium also inhibited the vascular permeability in mice. The aqueous solution of Bamboo salt inhibited the formation of ganuloma in SD rats at a oral dose of 1 g/kg. Angelica gigantis radix seems to have antiinflammatory effect by inhibition of PAF.

• 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]

• 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.

• Bulletin of the Korean Chemical Society
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• v.30 no.3
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• pp.707-709
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• 2009