• Archives of Plastic Surgery
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• v.36 no.1
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• pp.1-10
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• 2009

Purpose: Partial necrosis of skin flaps remains a substantial problem in reconstructive surgery. We investigated the potential use of an adenovirus vector encoding the VEGF, COMP-angiopoietin-1 gene in an attempt to promote the viability of the inferior epigastric artery flap in a rat model. Methods: Three by six cm lower abdominal transverse skin flaps, supplied only by the left inferior epigastric artery, were designed. After skin flap elevation, the adenovirus VEGF and adenovirus COMP-angiopoietin-1 were injected into the distal portion of the flap, which has a high tendency of developing flap ischemia. Control animals were injected with the same volume of normal saline. On 3, 7 and 14 days after the flap elevation, the flap survival and vascularization were assessed using Visitrak digital$^{(R)}$, CD31 immunohistochemistry in addition to evaluating the general histological characteristics. Results: There was a significant increase in the mean percentage of flap viability by 89.8%, 91.1% and 94.8% in flaps transfected with adenovirus VEGF, COMP-angiopoietin-1, coadministraion of VEGF and COMP-angiopoietin-1 at seven days, and by 95.6%, 94.8% and 96.3% at 14 days. Histological assessment revealed that there were more blood vessels formed after adenovirus with VEGF, COMP-angiopoietin-1 or VEGF plus COMP-angiopoietin-1 than with adenovirus Lac Z. Conclusion: The results of this study suggest that adenovirus-mediated VEGF, COMP-angiopoietin-1 gene therapy, promote therapeutic angiogenesis in patients that undergo reconstructive procedures.

• Journal of Oral Medicine and Pain
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• v.31 no.1
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• pp.17-25
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• 2006

The present study was undertaken to determine the possible cellular mechanism of action of angiopoietin-2 in bone metabolism. The effects on the osteoblasts were determined by measuring 1) cell viability, 2) alkaline phosphatase (ALP) activity, 3) gelatinase activity, and 4) nitric oxide production. The effects on the osteoclasts were investigated by measuring 1) tartrate-resistant acid phosphatase (TRAP)(+) multinucleated cells (MNCs) formation, and 2) resorption areas after culturing osteoclast precursors. Angiopoietin-2 treatment showed a significant increase in both the viability and ALP activity of osteoblasts. Angiopoietin-2 increased the activity of gelatinase and nitric oxide production. In addition, angiopoietin-2 decreased the osteoclast generation induced by macrophage-colony stimulating factor (M-CSF) and receptor activator of NF-kB ligand (RANKL), and inhibited osteoclastic activity in (M-CSF)-dependent bone marrow macrophage (MDBM) cell cultures. Taken these results, angiopoietin-2 may be a regulatory protein within the bone marrow microenvironment.

• The Journal of Korean Society for Radiation Therapy
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• v.12 no.1
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• pp.166-173
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• 2000

Angiopoietin-1(Ang-1) is a vasculogenic factor that signals through the endothelial cell-specific Tie2 receptor tyrosine kinase. We examined the effect of angiopoietin-1(Ang-1) on radiation-induced apoptosis in human umbilical vein endothelial cells(HUVECS) and receptor/second messenger signal transduction pathway for Ang-1's effect on HUVECs. The percent of apoptotic cells under control condition(0Gy) was $8.2\%$. Irradiation induced apoptosis was increased in a dose(1, 5, 10, and 15Gy)- and time 12, 24, 48 and 72hr)-dependent manner. The percent of apoptotic cells was approximately $34.9\%$ after 15 Gy of irradiation. Under these conditions, pretreatment with Ang-1's (50, 100, 200, and 400 ng/ml) inhibited irradiation-induced apoptosis in human umbilical vein endothelial cells in a dose-dependent manner. Two hundred ng/ml of Ang-1 inhibited approximately $55-60\%$ of the apoptotic events that occurred in the 10 Gy-irradiated cells. Pre-treatment with soluble Tie2 receptor, but not Tie1 receptor, blocked the Ang-1's antiapoptotic effects. Phosphatidylinositol 3'-kinase (P13-kinase) specific inhibitor, wortmanin and LY294002, blocked the Ang-1-induced antiapoptotic effect. Ang-1 promotes the survival of endothelial cells in irradiation-induced apoptosis through Tie2 receptor binding and P13-kinase activation. Pretreatment of Ang-1 could be beneficial in maintaining normal endothelial cell integrity during irradiation therapy.

• 한국약용작물학회:학술대회논문집
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• 2010.10a
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• pp.330-331
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• 2010

• Clinical and Experimental Reproductive Medicine
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• v.45 no.3
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• pp.143-148
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• 2018

Objective: The favored method of preserving fertility in young female cancer survivors is cryopreservation and autotransplantation of ovarian tissue. Reducing hypoxia until angiogenesis takes place is essential for the survival of transplanted ovarian tissue. The aim of this study was to investigate the role of angiopoietin-1 (Angpt-1), angiopoietin-2 (Angpt-2), and vascular endothelial growth factor (VEGF) in ovarian tissue grafts that were cryopreserved using two methods. Methods: Ovarian tissues harvested from ICR mice were divided into three groups: group I (control), no cryopreservation; group II, vitrification in EFS (ethylene-glycol, ficoll, and sucrose solution)-40; and group III, slow freezing in dimethyl sulfoxide. We extracted mRNA for VEGF, Angpt-1, and Angpt-2 from ovarian tissue 1 week following cryopreservation and again 2 weeks after autotransplantation. We used reverse transcriptase-polymerase chain reaction to quantify the levels of VEGF, Angpt-1, and Angpt-2 in the tissue. Results: Angpt-1 and Angpt-2 expression decreased after cryopreservation in groups II and III. After autotransplantation, Angpt-1 and Angpt-2 expression in ovarian tissue showed different trends. Angpt-1 expression in groups II and III was lower than in group I, but Angpt-2 in groups II and III showed no significant difference from group I. The vitrified ovarian tissues had higher expression of VEGF and Angpt-2 than the slow-frozen ovarian tissues, but the difference was not statistically significant. Conclusion: Our results indicate that Angpt-2 may play an important role in ovarian tissue transplantation after cryopreservation although further studies are needed to understand its exact function.

• Proceedings of the PSK Conference
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• 2002.04a
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• pp.178.2-179
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• 2002

• Asian Pacific Journal of Cancer Prevention
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• v.17 no.7
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• pp.3405-3409
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• 2016

Malignant pleural mesothelioma (MPM), an aggressive malignant tumor of mesothelial origin associated with asbestos exposure, shows a limited response to conventional chemotherapy and radiotherapy. Therefore, the overall survival of MPM patients remains very poor. Progress in the development of therapeutic strategies for MPM has been limited. We recently reported that the calpain inhibitor, calpeptin exerted inhibitory effects on pulmonary fibrosis by inhibiting the proliferation of lung fibroblasts. In the present study, we examined the preventive effects of calpeptin on the cell growth of MPM, the origin of which is mesenchymal cells, similar to lung fibroblasts. Calpeptin inhibited the proliferation of MPM cells, but not mesothelial cells. It also prevented 1) the expression of angiopoietin (Ang)-1 and Tie-2 mRNA in MPM cells, but not mesothelial cells and 2) the Ang-1-induced proliferation of MPM cells through an NF-kB dependent pathway, which may be the mechanism underlying the preventive effects of calpeptin on the growth of MPM cells. These results suggest potential clinical use of calpeptin for the treatment of MPM.

• Proceedings of the Korean Society of Applied Pharmacology
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• 2002.07a
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• pp.235-235
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• 2002

• Asian Pacific Journal of Cancer Prevention
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• v.16 no.18
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• pp.8579-8587
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• 2016

Background: The molecular mechanisms linking breast cancer progression and inflammation still remain obscure. The aim of the present study was to investigate the possible association of angiopoeitin like protein 4 (ANGPTL4) and its regulatory factor, hypoxia inducible factor-$1{\alpha}$ (HIF-$1{\alpha}$), with the inflammatory markers nuclear factor kappa B/p65 (NF-${\kappa}B$/P65) and interleukin-1 beta (IL-$1{\beta}$) in order to evaluate their role in inflammation associated breast cancer progression. Materials and Methods: Angiopoietin-like protein 4 (ANGPTL4) mRNA expressions were evaluated using quantitative real time PCR and its protein expression by immunohistochemistry. DNA binding activity of NF-${\kappa}B$/P65 was evaluated by transcription factor binding immunoassay. Serum levels of ANGPTL4, HIF-$1{\alpha}$ and IL-$1{\beta}$ were immunoassayed. Tumor clinico-pathological features were investigated. Results: ANGPTL4 mRNA expressions and serum levels were significantly higher in high grade breast carcinoma ($1.47{\pm}0.31$ and $184.98{\pm}18.18$, respectively) compared to low grade carcinoma ($1.21{\pm}0.32$ and $171.76{\pm}7.58$, respectively) and controls ($0.70{\pm}0.02$ and $65.34{\pm}6.41$, respectively), (p<0.05). Also, ANGPTL4 high/moderate protein expression was positively correlated with tumor clinico-pathological features. In addition, serum levels of HIF-$1{\alpha}$ and IL-$1{\beta}$ as well as NF-${\kappa}B$/P65 DNA binding activity were significantly higher in high grade breast carcinoma ($148.54{\pm}14.20$, $0.79{\pm}0.03$ and $247.13{\pm}44.35$ respectively) than their values in low grade carcinoma ( $139.14{\pm}5.83$, $0.34{\pm}0.02$ and $184.23{\pm}37.75$, respectively) and controls ($33.95{\pm}3.11$, $0.11{\pm}0.02$ and $7.83{\pm}0.92$, respectively), (p<0.001). Conclusion: ANGPTL4 high serum levels and tissue expressions in advanced grade breast cancer, in addition to its positive correlation with tumor clinico-pathological features and HIF-$1{\alpha}$ could highlight its role as one of the signaling factors involved in breast cancer progression. Moreover, novel correlations were found between ANGPTL4 and the inflammatory markers, IL-$1{\beta}$ and NF-${\kappa}B$/p65, in breast cancer, which may emphasize the utility of these markers as potential tools for understanding interactions for axes of carcinogenesis and inflammation contributed for cancer progression. It is thus hoped that the findings reported here would assist in the development of new breast cancer management strategies that would promote patients' quality of life and ultimately improve clinical outcomes. However, large-scale studies are needed to verify these results.

• Animal Bioscience
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• v.36 no.10
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• pp.1517-1529
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• 2023

Objective: The objective of this study was to investigate the phylogenetic and expression analysis of the angiopoietin-like (ANGPTL) gene family and their role in lipid metabolism in pigs. Methods: In this study, the amino acid sequence analysis, phylogenetic analysis, and chromosome adjacent gene analysis were performed to identify the ANGPTL gene family in pigs. According to the body weight data from 60 Jinhua pigs, different tissues of 6 pigs with average body weight were used to determine the expression profile of ANGPTL1-8. The ileum, subcutaneous fat, and liver of 8 pigs with distinct fatness were selected to analyze the gene expression of ANGPTL3, ANGPTL4, and ANGPTL8. Results: The sequence length of ANGPTLs in pigs was between 1,186 and 1,991 bp, and the pig ANGPTL family members shared common features with human homologous genes, including the high similarity of the amino acid sequence and chromosome flanking genes. Amino acid sequence analysis showed that ANGPTL1-7 had a highly conserved domain except for ANGPTL8. Phylogenetic analysis showed that each ANGPTL homologous gene shared a common origin. Quantitative reverse-transcription polymerase chain reaction analysis showed that ANGPTL family members had different expression patterns in different tissues. ANGPTL3 and ANGPTL8 were mainly expressed in the liver, while ANGPTL4 was expressed in many other tissues, such as the intestine and subcutaneous fat. The expression levels of ANGPTL3 in the liver and ANGPTL4 in the liver, intestine and subcutaneous fat of Jinhua pigs with low propensity for adipogenesis were significantly higher than those of high propensity for adipogenesis. Conclusion: These results increase our knowledge about the biological role of the ANGPTL family in this important economic species, it will also help to better understand the role of ANGPTL3, ANGPTL4, and ANGPTL8 in lipid metabolism of pigs, and provide innovative ideas for developing strategies to improve meat quality of pigs.