• 한국컴퓨터정보학회논문지
• /
• 제20권4호
• /
• pp.69-76
• /
• 2015

본 논문에서는 초분광 이미징시스템을 이용하여 획득된 헤모글로빈 포화이미지와 다양한 이미지프로세싱을 통해 얻어진 실시간 혈관 변화과정을 마이크로미터/밀리초 부터 밀리미터/시간에 이르는 시공간 해상도로 제공하여, 다양한 질병에 기인한 혈관의 생성 및 변화 등과 같은 고유한 생리적 특성뿐만 아니라 혈관간의 산소이동, 혈관질환의 치료효과의 검증 등 다목적 영상장비로의 개발이 가능하다. 이는 질병으로 인한 혈관의 변이과정을 관찰하기 위해 최근 다양한 임상 및 전임상 영상장비들이 개발되고 있으나 높은 개발비용과 환자들이 감수해야하는 위험부담에 비해 상대적으로 낮은 해상도와 제한된 만족도를 제공한다 한계점을 극복할 수 있다. 새로운 혈관의 생성 및 기존의 모세혈관 변화는 암 전이 및 발전과정 뿐만 아니라 다양한 질병의 종류에 따라 다른 특성을 보이며 이를 통한 생리학적 분석이 가능하므로 혈관의 연구를 통한 질병종류 및 유무의 판단은 진단 과정의 핵심 요소이며 새로운 치료법의 효과를 평가할 수 있는 중요한 근거가 될 것으로 기대한다.

• Archives of Plastic Surgery
• /
• 제44권2호
• /
• pp.95-100
• /
• 2017

Background Intima-to-intima microanastomotic vascular remodeling was explored, utilizing a polylactide-caprolactone absorbable vein coupler model (PAVCM), which was designed to simulate a non-absorbable counterpart system with the sole exception of being absorbable. Methods Six New Zealand white rabbits were used. After transection of the jugular vein, 2 PAVCMs were placed, 1 at each transected end. The stumps were slipped through the PAVCMs, and the venous wall was everted $90^{\circ}$ to achieve intima-to-intima contact. Reanastomosis of the transected jugular vein was performed bilaterally in 3 rabbits. In the other 3 rabbits, the jugular vein (20 mm) harvested from one side was interpositionally grafted to the jugular vein on the opposite side to ease the anastomotic tension. Patency testing, ultrasonography, and histologic assessments were conducted postoperatively at weeks 2, 4, 12, 16, 22, and 26. Results All anastomotic sites were patent, without stenosis, occlusion, or dilatation. In the histologic sections, immature endothelial regeneration was observed at week 2, which was completed by week 4. Regeneration of the tunica media was noted at week 12. Between week 22 and week 26, the tunica media fully regenerated and the coupler dissipated entirely. Conclusions Despite the absence of a coupler to act as an anastomotic buttress, the structure and function of all the vessels appeared normal, even histologically. These outcomes are true milestones in the development of an absorbable vein coupler.

• The Korean Journal of Physiology and Pharmacology
• /
• 제22권4호
• /
• pp.447-456
• /
• 2018

Angiotensin-(1-9) [Ang-(1-9)], generated from Ang I by Ang II converting enzyme 2, has been reported to have protective effects on cardiac and vascular remodeling. However, there is no report about the effect of Ang-(1-9) on pulmonary hypertension. The aim of the present study is to investigate whether Ang-(1-9) improves pulmonary vascular remodeling in monocrotaline (MCT)-induced pulmonary hypertensive rats. Sprague-Dawley rats received Ang-(1-9) ($576{\mu}g/kg/day$) or saline via osmotic mini-pumps for 3 weeks. Three days after implantation of osmotic mini-pumps, 50 mg/kg MCT or vehicle were subcutaneously injected. MCT caused increases in right ventricular weight and systolic pressure, which were reduced by co-administration of Ang-(1-9). Ang-(1-9) also attenuated endothelial damage and medial hypertrophy of pulmonary arterioles as well as pulmonary fibrosis induced by MCT. The protective effects of Ang-(1-9) against pulmonary hypertension were inhibited by Ang type 2 receptor ($AT_2R$) blocker, but not by Mas receptor blocker. Additionally, the levels of LDH and inflammatory cytokines, such as $TNF-{\alpha}$, MCP-1, $IL-1{\beta}$, and IL-6, in plasma were lower in Ang-(1-9) co-treated MCT group than in vehicle-treated MCT group. Changes in expressions of apoptosis-related proteins such as Bax, Bcl2, Caspase-3 and -9 in the lung tissue of MCT rats were attenuated by the treatment with Ang-(1-9). These results indicate that Ang-(1-9) improves MCT-induced pulmonary hypertension by decreasing apoptosis and inflammatory reaction via $AT_2R$.

• Tuberculosis and Respiratory Diseases
• /
• 제54권2호
• /
• pp.191-198
• /
• 2003

연구배경 : 기관지천식에서 기도 재구성과 관련되는 병리학적 소견은 다양하다. 본 연구의 목적은 기관지천식 환자의 기도내 혈관분포정도 및 다른 기도 재구성 소견과의 관련성을 일아보는데 있다. 방 법 : 기관지천식환자(n=34)와 대조군(n=6)을 대상으로 기관지점막조직생검을 시행하였다. HE 염색으로 기저막 및 기저막하부의 두께를, type IV collagen 면역염색을 하여 혈관분포정도(점막하 단위면적당 혈관의 수와 혈관면적)를 image analyzer를 이용 하여 측정하였다. 결 과 : 1) 기관지천식환자에서 대조군에 비해 기저막 두께 ($6.92{\pm}2.01{\mu}m$ vs $9.67{\pm}2.84{\mu}m$, p<0.05) 및 기저막하부의 두께 ($44.49{\pm}31.92{\mu}m$ vs $121.22{\pm}72.79{\mu}m$, p<0.05) 가 유의하게 높았다. 2) 기관지천식환자에서 대조군에 비해 점막하 단위면적당 혈관면적은 유의하게 높았으며 ($4.51{\pm}2.13%$ vs $10.32{\pm}6.08%$, p<0.05) 점막하 단위면적당 혈관수는 높은 경향을 보였으나 통계적인 유의성은 없었다. 3) 기관지천식환자에서 점막하 단위면적당 혈관면적 및 혈관수는 기저막 두께, 기저막하부의 두께, 기관지천식의 중증도, $FEV_1$, $PC_{20}$ 등과 유의한 상관관계가 없었다. 결 론 : 본 연구결과 혈관분포정도가 기관지천식환자의 기도 재구성에 중요한 요소임을 확인할 수 있었으나 다른 기도 재구성의 요소들과는 직접적인 관련성은 없었다. 따라서 각각의 기도 재구성의 요소들은 서로 다른 임상적인 의의를 가칠 것으로 사료되며 이러한 요소들에 대한 추후 연구가 필요할 것으로 생각된다.

• Tuberculosis and Respiratory Diseases
• /
• 제51권6호
• /
• pp.530-539
• /
• 2001

연구배경 : 기관지 천식은 기도의 재구성과 관련된 기도의 염증성 질환이다. Vascular endothelial growth factor(VEGF) 는 혈관생성과 염증반응에 관여하는 강력하고 다양한 기능의 사이토카인이며 Matrix metalloproteinase-9(MMP-9)은 기관지 천식에서 기도의 재구성을 일으키는 주요 단백분해 효소이다. 그러나, 아직 급성 기관지 천식에서 VEGF의 역할 및 VEGF와 MMP-9의 관련성등에 관한 보고는 거의 없다. 저자들은 급성 기관지 천식에서 VEGF가 기관지 염증반응에 관여하는지를 조사하였고 또한 객담내 VEGF 발현 정도와 MMP-9의 관련성도 같이 알아보고자 하였다. 방 법 : 저자들은 안정상태 및 급성천식상태 환자에서 객담내 VEGF와 MMP-9의 양을 효소 면역측정과 zymography 분석으로 측정하였고 또한 기관지 천식의 자발 발작시에도 측정하였다. 결 과 : 기관지 천식 환자군에서 안정상태의 천식환자군이나 건강 대조군보다 객담내 VEGF 양이 유의있게 높음을 알 수 있었고 또한 천식 발작시에는 안정시보다 더 유의있게 높았으며 천식치료후 점차 감소하였다. 급성 천식 환자들에서 객담내 VEGF농도는 호중구및 호산구들 수와 의의있게 관련이 있었고 또한 객담내 VEGF와 MMP-9의 농도사이에 유의있는 상관관계가 있음을 알 수 있었다. 결 론 : 급성 기관지 천식 환자에서 VEGF의 과도발현은 기도 염증반응과 관련이 있으며 또한 MMP-9과도 밀접한 연관성이 관련성이 있는 것으로 사료된다.

• Journal of the Korean Association of Oral and Maxillofacial Surgeons
• /
• 제31권5호
• /
• pp.363-369
• /
• 2005

Purpose: To determine the role of Insulin-like Growth Factor-I (IGF-I) in the regulation of Vascular Endothelial Growth Factor (VEGF) expression in MG-63 cells and then to find the mechanism b which this regulation occurs. Materials and methods: MG-63 cells were grown to confluence in 60-mm dishes. To determine the effects of IGF-I on expression of VEGF mRNA according to time and concentration, the cells were treated with 10 nM IGF-I, following isolation of total RNA and Northern blot analysis after 1, 2, 4, 8, 12, 24 hours and after 2 hours of treatment with 0.5, 2, 10, 25, 50 nM IGF-I respectively, isolation of total RNA and Northern blot analysis were followed. To determine the mechanism of action of IGF-I, inhibitors such as hydroxyurea $(76.1\;{\mu}g/ml)$, actinomycin D $(2.5\;{\mu}g/ml)$, cycloheximide $(10\;{\mu}g/ml)$ were added 1 hour after treatment of 10 nM IGF-I. Results: 1. the expression of VEGF mRNA was increased with treatment of IGF-I. 2. The expression of VEGF mRNA was increased according to time-and concentration dependent manner of IGF-I. 3. The effect of IGF-I was decreased by hydroxyuera, actinomycin D, but not by cycloheximide. Conclusion: IGF-I regulate the expression of VEGF mRNA in the level of DNA synthesis and transcription. These results could suggest that IGF-I plays an important role in angiogenesis in the process of new bone formation and remodeling.

• The Korean Journal of Physiology and Pharmacology
• /
• 제23권1호
• /
• pp.63-70
• /
• 2019

We aimed to propose a novel computational approach to predict the electromechanical performance of pre- and post-mitral valve cerclage annuloplasty (MVCA). Furthermore, we tested a virtual estimation method to optimize the left ventricular basement tightening scheme using a pre-MVCA computer model. The present model combines the three-dimensional (3D) electromechanics of the ventricles with the vascular hemodynamics implemented in a lumped parameter model. 3D models of pre- and post-MVCA were reconstructed from the computed tomography (CT) images of two patients and simulated by solving the electromechanical-governing equations with the finite element method. Computed results indicate that reduction of the dilated heart chambers volume (reverse remodeling) appears to be dependent on ventricular stress distribution. Reduced ventricular stresses in the basement after MVCA treatment were observed in the patients who showed reverse remodeling of heart during follow up over 6 months. In the case who failed to show reverse remodeling after MVCA, more virtual tightening of the ventricular basement diameter than the actual model can induce stress unloading, aiding in heart recovery. The simulation result that virtual tightening of the ventricular basement resulted in a marked increase of myocardial stress unloading provides in silico evidence for a functional impact of MVCA treatment on cardiac mechanics and post-operative heart recovery. This technique contributes to establishing a pre-operative virtual rehearsal procedure before MVCA treatment by using patient-specific cardiac electromechanical modeling of pre-MVCA.

• Genomics & Informatics
• /
• 제10권4호
• /
• pp.244-248
• /
• 2012

Oxidative stress, which results in an excessive product of reactive oxygen species (ROS), is one of the fundamental mechanisms of the development of hypertension. In the vascular system, ROS have physical and pathophysiological roles in vascular remodeling and endothelial dysfunction. In this study, ROS-hypertension-related genes were collected by the biological literature-mining tools, such as SciMiner and gene2pubmed, in order to identify the genes that would cause hypertension through ROS. Further, single nucleotide polymorphisms (SNPs) located within these gene regions were examined statistically for their association with hypertension in 6,419 Korean individuals, and pathway enrichment analysis using the associated genes was performed. The 2,945 SNPs of 237 ROS-hypertension genes were analyzed, and 68 genes were significantly associated with hypertension (p < 0.05). The most significant SNP was rs2889611 within MAPK8 (p = $2.70{\times}10^{-5}$; odds ratio, 0.82; confidence interval, 0.75 to 0.90). This study demonstrates that a text mining approach combined with association analysis may be useful to identify the candidate genes that cause hypertension through ROS or oxidative stress.

• Maxillofacial Plastic and Reconstructive Surgery
• /
• 제42권
• /
• pp.23.1-23.11
• /
• 2020

Background: 4-Hexylresorcinol (4HR) is able to increase angiogenesis. However, its molecular mechanism in the human endothelial cells has not been clarified. Methods: As endothelial cells are important in angiogenesis, we treated the human umbilical vein endothelial cells (HUVECs) with 4HR and investigated protein expressional changes by immunoprecipitation high-performance liquid chromatography (IP-HPLC) using 96 antisera. Results: Here, we found that 4HR upregulated transforming growth factor-β (TGF-β)/SMAD/vascular endothelial growth factor (VEGF) signaling, RAF-B/ERK and p38 signaling, and M2 macrophage polarization pathways. 4HR also increased expression of caspases and subsequent cellular apoptosis. Mechanistically, 4HR increased TGF-β1 production and subsequent activation of SMADs/VEGFs, RAF-B/ERK and p38 signaling, and M2 macrophage polarization. Conclusion: Collectively, 4HR activates TGF-β/SMAD/VEGF signaling in endothelial cells and induced vascular regeneration and remodeling for wound healing.

• Molecules and Cells
• /
• 제38권6호
• /
• pp.528-534
• /
• 2015

Hypoxia-inducible factor (HIF) is a key regulator of tumor growth and angiogenesis. Recent studies have shown that, BIX01294, a G9a histone methyltransferase (HMT)-specific inhibitor, induces apoptosis and inhibits the proliferation, migration, and invasion of cancer cells. However, not many studies have investigated whether inhibition of G9a HMT can modulate HIF-$1{\alpha}$ stability and angiogenesis. Here, we show that BIX01294 dose-dependently decreases levels of HIF-$1{\alpha}$ in HepG2 human hepatocellular carcinoma cells. The half-life of HIF-$1{\alpha}$, expression of proline hydroxylase 2 (PHD2), hydroxylated HIF-$1{\alpha}$ and von Hippel-Lindau protein (pVHL) under hypoxic conditions were decreased by BIX01294. The mRNA expression and secretion of vascular endothelial growth factor (VEGF) were also significantly reduced by BIX01294 under hypoxic conditions in HepG2 cells. BIX01294 remarkably decreased angiogenic activity induced by VEGF in vitro, ex vivo, and in vivo, as demonstrated by assays using human umbilical vein endothelial cells (HUVECs), mouse aortic rings, and chick chorioallantoic membranes (CAMs), respectively. Furthermore, BIX01294 suppressed VEGF-induced matrix metalloproteinase 2 (MMP2) activity and inhibited VEGF-induced phosphorylation of VEGF receptor 2 (VEGFR-2), focal adhesion kinase (FAK), and paxillin in HUVECs. In addition, BIX01294 inhibited VEGF-induced formation of actin cytoskeletal stress fibers. In conclusion, we demonstrated that BIX01294 inhibits HIF-$1{\alpha}$ stability and VEGF-induced angiogenesis through the VEGFR-2 signaling pathway and actin cytoskeletal remodeling, indicating a promising approach for developing novel therapeutics to stop tumor progression.