• BMB Reports
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• v.54 no.3
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• pp.170-175
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• 2021

Atherosclerosis arising from the pro-inflammatory conditions associated with chronic kidney disease (CKD) increases major cardiovascular morbidity and mortality. Rapamycin (RAPA) is known to inhibit atherosclerosis under CKD and non-CKD conditions, but it can cause dyslipidemia; thus, the co-application of lipid-lowering agents is recommended. Atorvastatin (ATV) has been widely used to reduce serum lipids levels, but its synergistic effect with RAPA in CKD remains unclear. Here, we analyzed the effect of their combined treatment on atherosclerosis stimulated by CKD in apolipoprotein E-deficient (ApoE-/-) mice. Oil Red O staining revealed that treatment with RAPA and RAPA＋ ATV, but not ATV alone, significantly decreased the atherosclerotic lesions in the aorta and aortic sinus, compared to those seen in the control (CKD) group. The co-administration of RAPA and ATV improved the serum lipid profile and raised the expression levels of proteins involved in reverse cholesterol transport (LXRα, CYP7A1, ABCG1, PPARγ, ApoA1) in the liver. The CKD group showed increased levels of various genes encoding atherosclerosispromoting cytokines in the spleen (Tnf-α, Il-6 and Il-1β) and aorta (Tnf-α and Il-4), and these increases were attenuated by RAPA treatment. ATV and RAPA＋ATV decreased the levels of Tnf-α and Il-1β in the spleen, but not in the aorta. Together, these results indicate that, in CKD-induced ApoE-/- mice, RAPA significantly reduces the development of atherosclerosis by regulating the expression of inflammatory cytokines and the co-application of ATV improves lipid metabolism.

• Korean Journal of Oriental Medicine
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• v.18 no.2
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• pp.131-137
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• 2012

Objectives : Primo vascular system is known to new circulatory system and suggested as a anatomical structure of meridian system. Primo-vessels are present throughout the whole body. The purpose of this study is to identify primo tissues taken from falciform ligament and to compare with organ surface primo tissue, blood vessel and lymph vessel. Methods : Male Sprague-Dawley rats (8weeks old, 250~320g) used for this study. The medial line of the abdomen was dissected and searched for primo tissues in falciform ligament and on the internal organs using stereomicroscope. We performed serial cross section and histological investigations. The tissues were stained with hematoxylin-eosin and Masson's trichrome. Results : 1. The primo tissues attached on the falciform ligament had white color and length of 5~8mm. 2. We could observe primo tissues are classified with ligament tissues. 3. Histologically, primo tissue on falciform ligament and organ surface primo tissue could be considered same tissue. Conclusions : In this study, we observed primo tissue discovered on the falciform ligament. And we also histologically compared such discovered primo tissue with organ surface primo tissue. Consequently, we could consider that two tissues have histological similarity and possibility of connection in one network system.

• Archives of Plastic Surgery
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• v.32 no.3
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• pp.327-334
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• 2005

This study was designed to investigate the effect of the surgical delay in the prefabricated cutaneous flap. Abdominal skin flaps (n=40), $4.5{\times}6.0cm$ in size, were created by the subcutaneous implantation of a saphenous vascular tissue in the male Sprague-Dawley rats. In the groups 1 and 2, the pedicle was skeletonized. In the groups 3 and 4, perivascular muscle cuff or gracilis fascia was retained, respectively. Six weeks later, each flap was elevated as an island flap and reposed in place. All flaps of the group 2 had a 72-hours of delay period. Five days after the flap repositioning, estimation of flap viability, microangiographies, and histological evaluation of vessel development were performed. The groups 2 and 3 showed higher viability in flap survival. The dilated choke vessels and fully developed vascular network were observed in the flap of the group 2, but not typically seen in the other groups. New vessels around the implanted pedicle were more developed in the group 2. Amount of the vessels in the mid-portion of the flap was significantly increased in the groups 2 and 4. In conclusion, the delay procedure enhanced the viability, and its effect was dependent on the new vessel formation around the implanted pedicle.

• Journal of Korean Academy of Oral and Maxillofacial Radiology
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• v.20 no.1
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• pp.41-49
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• 1990

The author observed the changes of vasculature of pre-and post-irradiation on DMBA induced rat tongue cancer. The study was performed by using vascular corrosion resin casting, and scanning electron microscopy. The results were as follows. 1. The capillaries runned parallely and formed bundles and, sometimes, plexus. The endothelial cells were arranged regularly and small pores were observed. 2. In irradiated normal tongue the capillaries were curved slightly and formed plexus on initial day of post-irradiation. On third day the capillaries and capillary pores were dilated and the endothelial cell arrangement was irregular. The effects of irradiation were gradually increased from initial to the 3rd day, though it was decreased after 7th day. 3. The vasculature of DMBA induced tongue cancer group were very irregular, and large avascular lesions were formed according to the cancer necrosis or tumor cell nest and the vasculature was narrowed and paralleled around the avascular lesion by compression of cancer cell nest. The vascular wall was roughened and dilated, forming club shaped or varix. 4. The vessels were curved and formed reticular network in irradiated DMBA induced tongue carinoma group. The free end of newly formed capillaries had regular width, and also irregular club shaped or aneurysmal dilatation were observed. The vascular structures were destroyed and vessels were fused in tumor necrosis lesion. The radiation effects were marked on the first and third day of irradiation and the effects were decreased after seventh day and showed capillary regeneration.

• IMMUNE NETWORK
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• v.11 no.6
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• pp.368-375
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• 2011

Background: Recent clinical observation reported that there was a significant correlation between change in circulating vascular endothelial growth factor (VEGF) levels and the occurrence of severe acute graft-versus-host disease (GVHD) following allogeneic hematopoietic stem cell transplantation (allo-HSCT), but the action mechanisms of VEGF in GVHD have not been demonstrated. Methods: This study investigated whether or not blockade of VEGF has an effect on acute GVHD in a lethally irradiated murine allo-HSCT model of $B6\;(H-2^b)\;{\rightarrow}B6D2F1\;(H-2^{b/d})$. Syngeneic or allogeneic recipient mice were injected subcutaneously with anti-VEGF peptides, dRK6 ($50{\mu}g/dose$) or control diluent every other day for 2 weeks (total 7 doses). Results: Administration of the dRK6 peptide after allo-HSCT significantly reduced survival with greaterclinical GVHD scores and body weight loss. Allogeneic recipients injected with the dRK6 peptide exhibited significantly increased circulating levels of VEGF and expansion of donor $CD3^+$ T cells on day +7 compared to control treated animals. The donor $CD4^+$ and $CD8^+$ T-cell subsets have differential expansion caused by the dRK6 injection. The circulating VEGF levels were reduced on day +14 regardless of blockade of VEGF. Conclusion: Together these findings demonstrate that the allo-reactive responses after allo-HSCT are exaggerated by the blockade of VEGF. VEGF seems to be consumed during the progression of acute GVHD in this murine allo-HSCT model.

• Archives of Plastic Surgery
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• v.37 no.6
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• pp.769-774
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• 2010

Purpose: As the soft tissue defect around the knee is difficult to reconstruct, local flap or free flap is used. Distally based anterolateral thigh pedicled flap introduced by Zhang uses sufficient reverse flow supplied from the vascular network around the knee. We report successful reconstruction of defect around knee by this method. Methods: Four patients with skin & soft tissue defect around knee have been treated for reconstruction using the distally based anterolateral thigh pedicled flap. First, the doppler was used to check the perforator flap of the descending branch of the lateral circumflex femoral artery and to draw and dissect the perforator flap as much as needed. After the dissection, the proximal of the descending branch was clamped and checked for sufficient supply of blood flow from the reverse flow and then ligated. It was dissected along the descending branch and in order to prevent damage to the joined parts of the descending branch and the lateral superior geniculate artery, a more careful ligation was done starting from 10 cm superior to the knee. The defect was reconstructed after securing enough vascular pedicle to cover all the damaged parts. Results: Not all patients suffered from flap necrosis. In case of the patient with chronic osteomyelitis, slight venous congestion was observed right after the surgery but it disappeared the following day. All three patients had no occurences of additional complications. Conclusion: Distally based anterolateral thigh pedicled flap was enough to provide large flap for knee reconstruction. It had sufficient blood flow and vascular pedicle. It also had taken short operation time compared to the free flap operation. The distally based anterolateral thigh pedicled flap used by the authors is a very useful way of reconstructing the area around knee.

• IMMUNE NETWORK
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• v.8 no.3
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• pp.75-81
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• 2008

Background: Platelets take part in repairing the lesions of endothelial damage. To understand the molecular mechanism of this process, we tested the hypothesis that CD154 expressed on activated platelets stimulates proliferation of human endothelial cells. Methods: The expression levels of CD154 and CD40 on platelets and endothelial cells, respectively, were measured by flow cytometry and confocal microscopy. Function-blocking monoclonal antibody against CD154 was developed after immunization with CD154-transfected L cells. Results: An anti-CD40 agonist antibody and soluble CD154 both induced significant proliferation of endothelial cells. In addition, a function-blocking anti-CD154 antibody inhibited the platelet-induced proliferation of endothelial cells, indicating that the CD154-CD40 pathway is involved in these cellular interactions. An anti-VEGF antibody failed to inhibit the proliferation. This, in addition to the fact that very small amounts of VEGF are released from platelets or endothelial cells, suggests that VEGF does not play an important role in the platelet-stimulated proliferation of endothelial cells. Conclusion: Our results indicate that platelets induce proliferation of endothelial cells by CD154-CD40 interactions independently of VEGF.

• BMB Reports
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• v.51 no.1
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• pp.21-26
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• 2018

Delta-like ligand 4 (DLL4) expression in endothelial cells is intimately associated with angiogenic sprouting and vascular remodeling, but the precise mechanism of transcriptional regulation of DLL4 remains incompletely understood. Here, we showed that LIM-domain binding protein 2 (LDB2) plays an important role in regulating basal DLL4 and VEGF-induced DLL4 expression. Knockdown of LDB2 using siRNA enhanced endothelial sprouting and tubular network formation in vitro. Injection of ldb2-morpholino resulted in defective development of intersegmental vessels in zebrafish. Reduction or over-expression of LDB2 in endothelial cells decreased or increased DLL4 expression. LDB2 regulated DLL4 promoter activity by binding to its promoter region and the same promoter region was occupied and regulated by the LMO2/TAL1/GATA2 complex. Interestingly, LDB2 also mediated VEGF-induced DLL4 expression in endothelial cells. The regulation of DLL4 by the LDB2 complex provides a novel mechanism of DLL4 transcriptional control that may be exploited to develop therapeutics for aberrant vascular remodeling.

• Journal of Korean Neurosurgical Society
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• v.62 no.2
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• pp.136-143
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• 2019

Moyamoya disease (MMD) is a progressive cerebrovascular disease with unknown etiology, characterized by bilateral steno-occlusive changes at the terminal portion of the internal carotid artery and an abnormal vascular network formation at the base of the brain. MMD has an intrinsic nature to convert the vascular supply for the brain from internal carotid (IC) system to the external carotid (EC) system, as indicated by Suzuki's angiographic staging. Insufficiency of this 'IC-EC conversion system' could result not only in cerebral ischemia, but also in intracranial hemorrhage from inadequate collateral anastomosis, both of which represent the clinical manifestation of MMD. Surgical revascularization prevents cerebral ischemic attack by improving cerebral blood flow, and recent evidence further suggests that extracranial-intracranial bypass could powerfully reduce the risk of re-bleeding in MMD patients with posterior hemorrhage, who were known to have extremely high re-bleeding risk. Although the exact mechanism underlying the hemorrhagic presentation in MMD is undetermined, most recent angiographic analysis revealed the characteristic angio-architecture related to high re-bleeding risk, such as the extension and dilatation of choroidal collaterals and posterior cerebral artery involvement. We sought to update the current management strategy for hemorrhagic MMD, including the outcome of surgical revascularization for hemorrhagic MMD in our institute. Further investigations will clarify the optimal surgical strategy to prevent hemorrhagic manifestation in patients with MMD.

• Journal of Interdisciplinary Genomics
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• v.4 no.2
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• pp.31-34
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• 2022

Background: Arteriovenous malformations (AVMs) are rare diseases comprising abnormally dilated arteries and veins with an absence of a capillary network. Since these diseases are intractable after diagnosis, various treatment strategies have been examined, with continuous efforts to identify target genes. Here, we report relevant new target genes selected via gene microarray. Methods: Endothelial cells were isolated from samples collected from three patients with AVM and three healthy individuals, followed by microarray analysis. Additionally, quantitative PCR was performed to select genes highly relevant to AVM. Results: In the vascular endothelial cells derived from the tissues of patients with AVM, the expression of ANGPT1, ANGPT2, DLL4, IL6, NRG1, TGFBR1, and VEGFA was typically higher compared to those derived from normal tissues. Conclusion: Seven candidate genes were selected to analyze the pathophysiological mechanism of AVM. These results may aid in future directions of diagnosis and treatment.