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Biomedical subjects

Mayumi Abe

Publications and source records attributed to Mayumi Abe.

18 recordsLinked to original sources
PubMed2006

Vasohibin prevents arterial neointimal formation through angiogenesis inhibition.

Vasohibin is a VEGF-inducible angiogenesis inhibitor in vascular endothelium. Here we examined the presence of vasohibin in human arterial wall, and found it in endothelium of adventitial microvessels in atherosclerotic lesion. Adventitial angiogenesis is involved in the progression of neointimal formation. Even in the presence of endogenous angiogenesis inhibitors, pathological angiogenesis persists. However, the supplementation of exogenous angiogenesis inhibitors can prevent pathological angiogenesis. We evaluated the potential role of vasohibin in neointimal formation. Adenovirus-mediated human vasohibin gene transfer in mouse liver resulted in the release of vasohibin in plasma and exhibited anti-angiogenic effects at remote sites. This gene transfer inhibited adventitial angiogenesis, macrophage infiltration, and neointimal formation after cuff placement on mouse femoral artery. Vasohibin exhibited no direct effect on migration and proliferation of smooth muscle cells. Thus, vasohibin has an activity to prevent neointimal formation by inhibiting adventitial angiogenesis.

Adult↗
PubMed2006

Isolation and characterization of vasohibin-2 as a homologue of VEGF-inducible endothelium-derived angiogenesis inhibitor vasohibin.

OBJECTIVE: We recently isolated vasohibin, a novel vascular endothelial growth factor (VEGF)-inducible endothelium-derived angiogenesis inhibitor. Our aim is to find DNA sequences homologous to vasohibin and determine their expression profile. METHODS AND RESULTS: By the search of DNA sequences in the database, we found one homologous gene and designated it vasohibin-2. Overall amino acid sequence homology between the prototype vasohibin (vasohibin-1) and vasohibin-2 was >50%. Vasohibin-2 exhibited antiangiogenic activity. Vasohibin-2 expression in cultured endothelial cells was low and not inducible by the stimulation that induced vasohibin-1. However, the immunohistochemical analysis revealed that vasohibin-1 and -2 were diffusely expressed in endothelial cells in embryonic organs during mid-gestation. After that time point, vasohibin-1 and -2 became faint, but persisted to a certain extent in arterial endothelial cells from late gestation to neonate. Expression of vasohibin-1 and -2 could be augmented in vivo by local transfection with the VEGF gene in the embryonic brain or by cutaneous wounding in adult mice. CONCLUSIONS: These results suggest that vasohibin-2, in combination with vasohibin-1, forms a novel family of angiogenesis inhibitors.

Angiogenesis Inhibitors↗
PubMed2005

Optimal control of ultrafast cis-trans photoisomerization of retinal in rhodopsin via a conical intersection.

Optimal control simulation is applied to the cis-trans photoisomerization of retinal in rhodopsin within a two-dimensional, two-electronic-state model with a conical intersection [S. Hahn and G. Stock, J. Phys. Chem. B 104, 1146 (2000)]. For this case study, we investigate coherent control mechanisms, in which laser pulses work cooperatively with a conical intersection that acts as a "wave-packet cannon." Optimally designed pulses largely consist of shaping subpulses that prepare a wave packet, which is localized along a reaction coordinate and has little energy in the coupling mode, through multiple electronic transitions. This shaping process is shown to be essential for achieving a high target yield although the envelopes of the calculated pulses depend on the local topography of the potential-energy surfaces around the conical intersection and the choice of target. The control mechanisms are analyzed by considering the motion of reduced wave packets in a nuclear configuration space as well as by snapshots of probability current-density maps.

Journal Article↗
PubMed2005

Raf-1 is a binding partner of DSCR1.

Down syndrome critical region 1 (DSCR1) is recognized as an endogenous calcineurin inhibitor. DSCR1 is induced in endothelial cells and may play an important role in inflammation and angiogenesis. To address a novel function of DSCR1, we searched interacting partners of DSCR1. We performed pull-down analysis using DSCR1 as a bait and identified Raf-1 as a binding partner. The association of Raf-1 was confirmed by co-immunoprecipitation in GM7373 cells expressing green fluorescence protein tagged DSCR1. We determined two Raf-1 binding regions in DSCR1; one in the N-terminus and the other in the C-terminus regions. We further demonstrated that calpain cleaved DSCR1 and generated fragments with different binding affinity to Raf-1 or calcineurin. These results constitute the first demonstration of Raf-1 as a binding partner of DSCR1, and suggest a novel role of DSCR1.

Binding Sites↗
PubMed2005

Gene regulation of a novel angiogenesis inhibitor, vasohibin, in endothelial cells.

We recently reported that vasohibin is a negative feedback regulator of angiogenesis, and it is specifically expressed in endothelial cells. Here, we characterize the regulation of vasohibin expression. Two possible splicing variants were found, and the longer isoform was preferentially expressed. VEGF induced the expression of vasohibin, and this induction was abrogated by anti-VEGFR2 mAb but not by anti-VEGFR1 mAb. Pharmacological analysis revealed that the downstream targets of VEGFR2 were PKCs, especially PKCdelta. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon VEGF treatment, whereas cycloheximide completely abolished its induction. We tested the effect of various inflammatory cytokines on vasohibin expression. TNFalpha, IL1 and IFNgamma decreased VEGF-stimulated vasohibin expression. Actinomycin D did not alter the kinetics of vasohibin mRNA induction upon TNFalpha treatment. These results indicate that the expression of vasohibin in endothelial cells is regulated either positively or negatively by certain factors at the transcriptional level.

Angiogenesis Inhibitors↗
PubMed2005

The Buen Pastor cemetery in Trujillo, Venezuela: measuring dengue vector output from a public area.

As vector control of dengue typically targets individual households to eliminate breeding sites or control adult mosquitoes during epidemics, public spaces are frequently neglected. To investigate the importance of such places as sources of dengue vectors, a study of Aedes aegypti productivity in a cemetery in northern Venezuela, using standard entomological indices for assessing dengue vector infestations, was carried out in the wet season in May 2003. Containers were found on 72.8% of graves; 44% of the containers held water and in 46.9% of these we found A. aegypti larvae and/or pupae. The average density of Aedes-infested containers was 39 per hectare. There were no significant differences in infestation rates between container types (vases, planters or others) or materials (cement, plastic, glass, etc.). Containers with 1-5 l of water held the greatest proportion of the pupae found in the cemetery (46.7%); containers with <100 ml of water contained no pupae. The mean number of pupae produced in the cemetery was estimated at 4185 pupae/ha per 48 h and the daily output of potential vector mosquitoes from the entire cemetery was calculated at approximately 3000 females per day. These mosquitoes presumably left the cemetery to feed in the nearby communities, thus thwarting the environmental management and health education programmes that had reduced household dengue vector infestations. The study shows the importance of public places as sources of dengue vectors in urban areas, and the need to include such areas in vector control programmes.

Aedes↗
PubMed2004

Down syndrome candidate region 1,a downstream target of VEGF, participates in endothelial cell migration and angiogenesis.

Vascular endothelial growth factor (VEGF) is a principal stimulator of angiogenesis. However, the downstream targets of VEGF in endothelial cells (ECs) are not entirely clarified. Survey of downstream targets of VEGF in human ECs identified a number of genes, including Down syndrome candidate region 1 (DSCR1). Here, we confirmed the inducible expression of DSCR1 in ECs by Northern and Western blottings. Moreover, VEGF-stimulated induction of DSCR1 was blocked by anti-VEGF receptor-2 monoclonal antibody (mAb), or the specific calcineurin inhibitors cyclosporin A and FK506. The expression of DSCR1 in ECs of neovessels was further shown by immunohistochemical analysis. We therefore examined whether DSCR1 played any roles in angiogenesis. The specific downregulation of DSCR1 expression by antisense oligonucleotide (AS-ODN) inhibited VEGF-stimulated migration of ECs as well as angiogenesis in vivo. AS-ODN inhibited the spreading of ECs on vitronectin, as well as on the immobilized anti-alphavbeta3 mAb, but not on anti-alphavbeta5 mAb. Moreover, AS-ODN inhibited tyrosine phosphorylation of focal adhesion kinase when ECs were plated on a vitronectin-coated dish. Immunoprecipitation followed by Western blotting showed the coimmunoprecipitation of DSCR1 and integrin alphavbeta3. These results suggest that DSCR1 is involved in angiogenesis by regulating adhesion and migration of ECs via the interaction with integrin alphavbeta3.

Cell Movement↗
PubMed2004

Transcriptional regulation of angiogenesis-related puromycin-insensitive leucyl-specific aminopeptidase in endothelial cells.

Puromycin-insensitive leucyl-specific aminopeptidase (PILSAP) was expressed in endothelial cells (ECs) and played an important role in angiogenesis. Here, we characterized its transcriptional regulation. Mouse PILSAP gene contained 19 exons and located in the chromosome 13C1-C2. We identified two transcripts; one transcribed from exon 1 and the other from exon 2. Mouse ECs expressed dominantly the one from exon 1. The promoter analysis using 5' upstream region of exon 1 revealed that -1868 to -1812 was critical for its transcription in mouse ECs. We identified a motif of the transcription factor PEBP2 in this region, and the deletion or mutation of this motif decreased promoter activity. Protein extracted from mouse ECs bound specifically to this motif. AML1/Runx1/PEBP2alphaB increased PILSAP mRNA in mouse ECs, whereas dominant interfering chimerical PEBP2beta-MYH11 decreased it. These results indicate that the expression of PILSAP in mouse ECs is regulated, at least in part, by PEBP2.

Animals↗
PubMed2004

Transcriptional regulation of human angiopoietin-2 by transcription factor Ets-1.

Angiopoietin-2 (Ang-2) plays an important role in destabilizing vessels for angiogenesis, however its transcriptional regulation has not been determined. Here we isolated about 3.2kb of the 5' upstream of the human Ang-2 gene and further characterized the transcriptional regulation of Ang-2. We found 10 Ets binding sites (EBSs) in this region. Ets-1 and Ets-2 but not Erg-1 augmented its promoter activity. Sequential deletion of EBSs and mutation analysis revealed that EBS8 located at -416/-406 from the translation initiation site was critical for Ets-1- or Ets-2-stimulated promoter activity. VEGF induced the expression of Ets-1 and Ang-2 in human umbilical vein endothelial cells (HUVECs). Electrophoretic mobility shift and chromatin immunoprecipitation assays showed that Ets-1 bound to EBS8 in HUVECs. Moreover, synthetic double-strand oligonucleotides containing corresponding EBS8 abrogated the induction of Ang-2 by VEGF in HUVECs. These results indicate that Ets-1 and the corresponding EBS are critical for the induction of Ang-2.

Angiopoietin-2↗
PubMed2004

Vascular endothelial zinc finger 1 is involved in the regulation of angiogenesis: possible contribution of stathmin/OP18 as a downstream target gene.

OBJECTIVE: Vascular endothelial zinc finger 1 (Vezf1) is a recently identified zinc finger transcription factor that is expressed in endothelial cells (ECs) during vascular development in mouse embryo. Here, we present that Vezf1 was expressed in ECs at the site of postnatal angiogenesis. We therefore examined whether Vezf1 was involved in the regulation of angiogenesis. METHODS AND RESULTS: The specific downregulation of Vezf1 by antisense oligodeoxynucleotide (AS-ODN) significantly inhibited the proliferation, migration, and network formation of cultured ECs as well as angiogenesis in vivo. Vezf1 AS-ODN downregulated the expression of stathmin/oncoprotein18 (OP18), a microtubule-destabilizing protein, in ECs, whereas transient transfection of Vezf1 cDNA increased the expression of stathmin/OP18 in ECs. To explore the relationship between Vezf1 and stathmin/OP18, we specifically downregulated stathmin/OP18. We found that stathmin/OP18 AS-ODN inhibited the proliferation, migration, and network formation of ECs as Vezf1 AS-ODN did. Moreover, Vezf1 AS-ODN decreased G2/M population of ECs and increased apoptosis, which reproduced the characteristic feature of stathmin/OP18 inhibition. CONCLUSIONS: These results suggest that Vezf1 is involved in the regulation of angiogenesis, at least in part, through the expression of stathmin/OP18 in ECs.

Animals↗
PubMed2004

Reliability and validity of the Japanese version of the Support Team Assessment Schedule (STAS-J).

OBJECTIVE: The aim of this project was to develop an appropriate and valid instrument for assessment by medical professionals in Japanese palliative care settings. METHODS: We developed a Japanese version of the Support Team Assessment Schedule (STAS-J), using a back translation method, and tested its reliability and validity. In the reliability study, 16 nurses and a physician who work in a palliative care unit evaluated 10 hypothetical cases twice at 3-month intervals. For the validity study, external researchers interviewed 50 patients with matignancy and their families and compared the results with ratings by the nurses in the palliative care unit. RESULTS: Our results with hypothetical cases were: interrater reliability weighted kappa = 0.53-0.77 and intrarater reliability weighted kappa = 0.64-0.85. In the validity study comparing nurse evaluations and the results of interviews with patients and families, complete agreement was 36-70%, and close agreement (+/-1) was 74-100%. As a whole, weighted kappa were low: between -0.07 and 0.51. Our results were similar to those in the United Kingdom and Canada. SIGNIFICANCE OF RESULTS: Although this research was conducted under methodologically limited conditions, we concluded that the STAS-J is a reliable tool and its validity is acceptable. The STAS-J should become a valuable tool, not only for daily clinical use, but also for research.

Adult↗
PubMed2004

Vasohibin as an endothelium-derived negative feedback regulator of angiogenesis.

Negative feedback is a crucial physiological regulatory mechanism, but no such regulator of angiogenesis has been established. Here we report a novel angiogenesis inhibitor that is induced in endothelial cells (ECs) by angiogenic factors and inhibits angiogenesis in an autocrine manner. We have performed cDNA microarray analysis to survey VEGF-inducible genes in human ECs. We characterized one such gene, KIAA1036, whose function had been uncharacterized. The recombinant protein inhibited migration, proliferation, and network formation by ECs as well as angiogenesis in vivo. This inhibitory effect was selective to ECs, as the protein did not affect the migration of smooth muscle cells or fibroblasts. Specific elimination of the expression of KIAA1036 in ECs restored their responsiveness to a higher concentration of VEGF. The expression of KIAA1036 was selective to ECs, and hypoxia or TNF-alpha abrogated its inducible expression. As this molecule is preferentially expressed in ECs, we designated it "vasohibin." Transfection of Lewis lung carcinoma cells with the vasohibin gene did not affect the proliferation of cancer cells in vitro, but did inhibit tumor growth and tumor angiogenesis in vivo. We propose vasohibin to be an endothelium-derived negative feedback regulator of angiogenesis.

Amino Acid Sequence↗
PubMed2003

HEX acts as a negative regulator of angiogenesis by modulating the expression of angiogenesis-related gene in endothelial cells in vitro.

OBJECTIVE: The hematopoietically expressed homeobox (HEX) is transiently expressed in endothelial cells (ECs) during vascular formation in embryo. Here, we investigated whether HEX played any role in angiogenesis-related properties of ECs in vitro. METHODS AND RESULTS: We transiently overexpressed HEX in human umbilical vein ECs (HUVECs). To our surprise, HEX completely abrogated the response of HUVECs to vascular endothelial growth factor (VEGF) with regard to proliferation, migration, and invasion and abolished network formation by HUVECs on Matrigel. cDNA microarray analysis and quantitative real-time reverse transcription-polymerase chain reaction combined with Western blotting revealed that HEX significantly repressed the expression of VEGF receptor-1, VEGF receptor-2, neuropilin-1, tyrosine kinase with Ig and EGF homology domains (TIE)-1, TIE-2, and the integrin alpha(v) subunit, whereas it augmented the expression of endoglin in HUVECs. We established murine embryonic stem cells that were stably transfected with HEX sense cDNA or antisense cDNA, and we examined the in vitro differentiation to ECs. Although the expression of VEGF receptor-2 was decreased in sense transfectants, the number of cells expressing VE-cadherin, a specific marker of ECs, was not altered. CONCLUSIONS: Our present results suggest that HEX may not affect the differentiation of ECs but acts as a negative regulator of angiogenesis.

Animals↗
PubMed2002

Goniodomin A, an antifungal polyether macrolide, exhibits antiangiogenic activities via inhibition of actin reorganization in endothelial cells.

Goniodomin A (GDA) is an antifungal polyether macrolide isolated from the dinoflagellate Goniodoma pseudogoniaulax. Previous studies revealed that GDA profoundly affected cytoskeletal reorganization. We examined the effect of GDA on the angiogenic properties of vascular endothelial cells. GDA itself did not affect proliferation of, migration of, and tube formation in type I collagen gels by, bovine aortic endothelial cells (BAECs). Proliferation of BAECs stimulated by bFGF was not affected by GDA at concentrations of up to 10 nM. However, at similar concentrations, GDA significantly inhibited bFGF-induced migration and tube formation in type I collagen gels by BAECs. Actin reorganization is required for cell migration. GDA caused the perinuclear aggregation of filamentous actin and inhibited stress fiber formation in bFGF- or VEGF-stimulated BAECs and lysophosphatidic acid-stimulated HeLa cells. However, GDA did not affect stress fiber structures already formed through Gbetagamma expression or in constitutively active RhoA mutant HeLa cells. Finally, GDA inhibited forming of vasucular system in a chorioallantoic membrane. Our results indicated that GDA suppressed angiogenic properties of ECs at least in part through the inhibition of actin reorganization and inhibited angiogenesis in vivo.

Actin Cytoskeleton↗
PubMed2002

Puromycin insensitive leucyl-specific aminopeptidase (PILSAP) is involved in the activation of endothelial integrins.

We previously reported that mouse orthologue of puromycin insensitive leucyl-specific aminopeptidase (mPILSAP) played an important role in angiogenesis by regulating the proliferation and migration of endothelial cells (ECs) (Miyashita et al., 2002. Blood 99:3241-3249). Here, we examined the mechanism as to how mPILSAP regulates the migration of ECs. Cell adhesion through integrins plays a crucial role in cell migration, and ECs use at least type-1 collagen receptor integrin alpha2beta1, fibronectin receptor alpha5beta1, and vitronectin receptors alphavbeta3 and alphavbeta5. mPILSAP antisense oligodeoxynucleotide (AS-ODN) or leucinethiol (LT), a leucyl-aminopeptidase inhibitor, did not affect the attachment but did significantly inhibit the spreading of cells of the murine endothelial cell line MSS31 when they were plated on vitronectin-, fibronectin-, or type-1 collagen, although they did not affect the expression of integrin alpha2, alpha5, alphav, beta1, beta3, and beta5 subunits on the cell surface. AS-ODN and LT also inhibited the tyrosine phosphorylation of FAK when cells were plated on vitronectin, fibronectin, or type-1 collagen. This inhibition of cell spreading and of tyrosine phosphorylation of FAK could be negated by Mg(2+). These results suggest that mPILSAP is involved in the activation of endothelial integrins.

Androstadienes↗
PubMed2001

Involvement of Fas/Fas ligand system in the spinal cords of HTLV-I-associated myelopathy.

To investigate whether the Fas/Fas ligand (FasL) system is involved in the pathogenesis of HTLV-I associated myelopathy (HAM), expression of Fas/FasL in the spinal cord lesions of HAM patients was examined by immunohistochemistry and reverse transcription polymerase chain reaction (RT-PCR). Fas was preferentially expressed on infiltrating T cells in active-chronic lesions of HAM. FasL expression was up-regulated on various cells, mainly microglia/macrophages in active-chronic lesions. In contrast, Fas expression was markedly down-regulated in inactive-chronic lesions of HAM patients who had a long duration of illness. The expressions of Fas/FasL in inactive-chronic lesions were comparable to those of normal controls. In normal controls, vascular endothelial cells constitutively displayed both Fas and FasL immunoreactivity, while microglia expressed FasL. RT-PCR confirmed constitutive expression of both Fas mRNA and FasL mRNA in the spinal cords of HAM patients, and in controls. Our results indicate that Fas/FasL system is involved in the inflammatory process in the central nervous system of HAM patients.

Adult↗
PubMedDate not supplied

MS-818 accelerates mobilization of endothelial progenitor cells and differentiation to endothelial cells.

MS-818 that is a synthetic pyrimidine compound and shown to have neurotrophic actions, enhanced basic fibroblast growth factor (bFGF)-induced angiogenesis in vivo. However, the mechanism and whether MS-818 affects endothelial cells (ECs) directly is not known. Here, the authors investigated whether MS-818 alone could induce angiogenesis and tried to clarify the mechanism of neovascularization by MS-818 in terms of angiogenesis and vasculogenesis. The authors show that MS-818 affects ECs directly and induces migration of and tube formation by ECs in vitro (angiogenesis). Furthermore, the authors demonstrate that MS-818 mobilizes endothelial progenitor cells (EPCs) from the bone marrow and potentiates their differentiation to ECs (vasculogenesis). The effect of MS-818 on the endothelial differentiation was further confirmed with an in vitro differentiation system using mouse embryonic stem cells. MS-818 activates the mitogen-activated protein kinase (MAPK) pathway but not the phosphoinositol 3-kinase (PI3K)-Akt pathway in ECs. These results indicate that MS-818, a synthetic compound, promotes both angiogenesis and vasculogenesis.

Animals↗